Numerous pathological states of the nervous system involve alterations in neuronal excitability and synaptic dysfunction,which depend on the function of ion channels.Due to their critical involvement in health and dis...Numerous pathological states of the nervous system involve alterations in neuronal excitability and synaptic dysfunction,which depend on the function of ion channels.Due to their critical involvement in health and disease,the search for new compounds that modulate these proteins is still relevant.Traditional medicine has long been a rich source of neuroactive compounds.For example,the indigenous Mapuche people have used the leaves and bark of the Drimys winteri tree for centuries to treat various diseases.Consequently,several studies have investigated the biological effects of compounds in Drimys winteri,highlighting sesquiterpenes such asα-humulene,drimenin,polygodial,andα-,β-,γ-eudesmol.However,there is currently no literature review focusing on the ability of these sesquiterpenes to modulate ion channels.This review summarizes the current knowledge about neuroactive compounds found in Drimys winteri,with special emphasis on their direct actions on neuronal ion channels.Several Drimys winteri sesquiterpenes modulate a diverse array of neuronal ion channels,including transient receptor potential channels,gamma-aminobutyric acid A receptors,nicotinic acetylcholine receptors,and voltage-dependent Ca^(2+)and Na^(+)channels.Interestingly,the modulation of these molecular targets by Drimys winteri sesquiterpenes correlates with their therapeutic actions.The promiscuous pharmacological profile of Drimys winteri sesquiterpenes suggests they modulate multiple protein targets in vivo,making them potentially useful for treating complex,multifactorial diseases.Further studies at the molecular level may aid in developing multitargeted drugs with enhanced therapeutic effects.展开更多
The ion channel in neurons is the basic component of signal transmission in the nervous system.The ion channel has important effects on the potential of neuron release and dynamic behavior in neural networks.Ion chann...The ion channel in neurons is the basic component of signal transmission in the nervous system.The ion channel has important effects on the potential of neuron release and dynamic behavior in neural networks.Ion channels control the flow of ions into and out of the cell membrane to form an ion current,which makes the excitable membrane produce special potential changes and become the basis of nerve and muscle activity.The blockage of ion channels has a significant effect on the dynamics of neurons and networks.Therefore,it is very meaningful to study the influence of ion channels on neuronal dynamics.In this work,a hybrid ion channel is designed by connecting a charge-controlled memristor(CCM)with an inductor in series,and a magnetic flux-controlled memristor(MFCM),capacitor,and nonlinear resistor are connected in parallel with the mixed ion channel to obtain the memristor neural circuit.Furthermore,the oscillator model with a hybrid ion channel and its energy function are calculated,and a map neuron is obtained by linearizing the neuron oscillator model.In addition,an adaptive regulation method is designed to explore the adaptive regulation of energy on the dynamic behaviors of the map neuron.The results show that the dynamics of a map neuron with a hybrid ion channel can be controlled by parameters and external magnetic fields.This study is also used to research synchronization between map neurons and collective behaviors in the map neurons network.展开更多
The inherent safety,high theoretical specific capacity and low raw material cost of aqueous batteries make them potential candidates in large-scale energy storage.However,uncontrolled dendrite growth,parasitic reactio...The inherent safety,high theoretical specific capacity and low raw material cost of aqueous batteries make them potential candidates in large-scale energy storage.However,uncontrolled dendrite growth,parasitic reactions and sluggish mass transfer on the anode-electrolyte interface are the main challenges restricting the application prospect of aqueous zinc-ion batteries.In general,eukaryotic cells utilize specific ion channels to achieve ion migration with the merits of low energy consumption and rapid speed.Herein,migrating the concept of ion channels to aqueous batteries,a crown species encapsulated zeolitic imidazolate framework(ZIF)interfacial layer(denoted as ZIF@Crown)was ex situ decorated onto the Zn anode.Similar to biological ion channels,the ZIF@Crown layer can homogenize the distribution of Zn^(2+)on the anode,accelerate the desolvation of hydrated Zn^(2+)and reduce the energy barrier for Zn^(2+)deposition,which were verified by theoretical calculations and experimental characterizations.Benefiting from these efficacious modulation mechanisms,the Zn@ZIF@Crown symmetrical cell could achieve a long calendar life of over 1900 h and the Zn@ZIF@Crown||Cu also sustained 600 cycles with a high Coulombic efficiency(97%).Furthermore,the full cells containing ZIF@Crown layer exhibit desirable electrochemical performance.This work provides an innovative avenue toward the optimization of aqueous batteries via bionic interfacial engineering.展开更多
The authors used suspension cells of Populus euphratica to isolate protoplast in the present study. Protoplasts were successfully obtained after 4 hours incubation in enzyme solution containing 1 0% cellulase “o...The authors used suspension cells of Populus euphratica to isolate protoplast in the present study. Protoplasts were successfully obtained after 4 hours incubation in enzyme solution containing 1 0% cellulase “onozuka” R\|10, 0\^01% pectolyase Y\|23,0\^15% macerozyme R\|10 and 0\^1% hemicellulase at 25℃. Outward and inward single channels in plasma membrane were observed using cell\|attached recording of patch\|clamp technique. In this study, single channel records showed that more than one species of channel were obtained. These attempts in protoplast isolation and ion channel recording offers the opportunity to characterize cellular mechanisms of salt tolerance in tree species.展开更多
Cyclic nucleotide-gated ion channels （CNGs） are distributed most widely in the neuronal cell. Great progress has been made in molecular mechanisms of CNG channel gating in the recent years. Results of many experimen...Cyclic nucleotide-gated ion channels （CNGs） are distributed most widely in the neuronal cell. Great progress has been made in molecular mechanisms of CNG channel gating in the recent years. Results of many experiments have indicated that the stoichiometry and assembly of CNG channels affect their property and gating. Experiments of CNG mutants and analyses of cys- teine accessibilities show that cyclic nucleotide-binding domains （CNBD） bind cyclic nucleotides and subsequently conformational changes occurred followed by the concerted or cooperative conformational change of all four subunits during CNG gating. In order to provide theoretical assistances for further investigation on CNG channels, especially regarding the disease pathogenesis of ion channels, this paper reviews the latest progress on mechanisms of CNG channels, functions of subunits, processes of subunit assembly, and conformational changes of subunit regions during gating.展开更多
Objective To re-confirm and characterize the biophysical and pharmacological properties of endogenously expressed human acid-sensing ion channel 1a （hASIC1a） current in HEK293 cells with a modified perfusion methods...Objective To re-confirm and characterize the biophysical and pharmacological properties of endogenously expressed human acid-sensing ion channel 1a （hASIC1a） current in HEK293 cells with a modified perfusion methods. Methods With cell floating method, which is separating the cultured cell from coverslip and putting the cell in front of perfusion tubing, whole cell patch clamp technique was used to record hASICla currents evoked by low pH external solution. Results Using cell floating method, the amplitude of hASICla currents activated by pH 5.0 in HEK293 cells is twice as large as that by the conventional method where the cells remain attached to coverslip. The time to reach peak at two different recording conditions is （21±5） ms and （270±25） ms, respectively. Inactivation time constants are （496±23） ms and （2284±120） ms, respectively. The cell floating method significantly increases the amiloride potency of block on hASIC 1 a [IC50 is （3.4± 1.1 ） μmol/L and （2.4± 0.9） μmol/L, respectively]. Both recording methods have similar pH activation ECs0 （6.6±0.6, 6.6±0.7, respectively）. Conclusion ASICs channel activation requires fast exchange of extracellular solution with the different pH values. With cell floating method, the presence of hASIC la current was re-confirmed and the biophysical and pharmacological properties of hASIC la channel in HEK293 cells was precisely characterized. This method could be used to study all ASICs and other ligand-gated channels that require fast extracellular solution exchange.展开更多
Ion channels are crucial in the generation and modulation of excitability in the nervous system and have been implicated in human epilepsy. Forty-one epilepsyassociated ion channel genes and their mutations are system...Ion channels are crucial in the generation and modulation of excitability in the nervous system and have been implicated in human epilepsy. Forty-one epilepsyassociated ion channel genes and their mutations are systematically reviewed. In this paper, we analyzed the genotypes, functional alterations（funotypes）, and phenotypes of these mutations. Eleven genes featured loss-offunction mutations and six had gain-of-function mutations.Nine genes displayed diversified funotypes, among which a distinct funotype-phenotype correlation was found in SCN1A. These data suggest that the funotype is an essential consideration in evaluating the pathogenicity of mutations and a distinct funotype or funotype-phenotype correlation helps to define the pathogenic potential of a gene.展开更多
Sexually reproducing animals require an orchestrated communication between spermatozoa and the egg to generate a new individual. Capacitation, a maturational complex phenomenon that occurs in the female reproductive t...Sexually reproducing animals require an orchestrated communication between spermatozoa and the egg to generate a new individual. Capacitation, a maturational complex phenomenon that occurs in the female reproductive tract, renders spermatozoa capable of binding and fusing with the oocyte, and it is a requirement for mammalian fertilization. Capacitation encompasses plasma membrane reorganization, ion permeability regulation, cholesterol loss and changes in the phosphorylation state of many proteins. Novel tools to study sperm ion channels, image intracellular ionic changes and proteins with better spatial and temporal resolution, are unraveling how modifications in sperm ion transport and phosphorylation states lead to capacitation. Recent evidence indicates that two parallel pathways regulate phosphorylation events leading to capacitation, one of them requiring activation of protein kinase A and the second one involving inactivation of ser/thr phosphatases. This review examines the involvement of ion transporters and phosphorylation signaling processes needed for spermatozoa to achieve capacitation. Understanding the molecular mechanisms leading to fertilization is central for societies to deal with rising male infertility rates, to develop safe male gamete-based contraceptives and to preserve biodiversity through better assisted fertilization strategies.展开更多
Neuropathic pain(NPP)is a kind of pain caused by disease or damage impacting the somatosensory system.Ion channel drugs are the main treatment for NPP;however,their irregular usage leads to unsatisfactory pain relief....Neuropathic pain(NPP)is a kind of pain caused by disease or damage impacting the somatosensory system.Ion channel drugs are the main treatment for NPP;however,their irregular usage leads to unsatisfactory pain relief.To regulate the treatment of NPP with ion channel drugs in clinical practice,the Chinese Association for the Study of Pain organized first-line pain management experts from China to write an expert consensus as the reference for the use of ion channels drugs.Here,we reviewed the mechanism and characteristics of sodium and calcium channel drugs,and developed recommendations for the therapeutic principles and clinical practice for carbamazepine,oxcarbazepine,lidocaine,bulleyaconitine A,pregabalin,and gabapentin.We hope this guideline provides guidance to clinicians and patients on the use of ion channel drugs for the management of NPP.展开更多
Diabetes mellitus affects the heart through various mechanisms such as microvascular defects,metabolic abnormalities,autonomic dysfunction and incompatible immune response.Furthermore,it can also cause functional and ...Diabetes mellitus affects the heart through various mechanisms such as microvascular defects,metabolic abnormalities,autonomic dysfunction and incompatible immune response.Furthermore,it can also cause functional and structural changes in the myocardium by a disease known as diabetic cardiomyopathy(DCM)in the absence of coronary artery disease.As DCM progresses it causes electrical remodeling of the heart,left ventricular dysfunction and heart failure.Electrophysiological changes in the diabetic heart contribute significantly to the incidence of arrhythmias and sudden cardiac death in diabetes mellitus patients.In recent studies,significant changes in repolarizing K+currents,Na+currents and L-type Ca^(2+)currents along with impaired Ca^(2+ )homeostasis and defective contractile function have been identified in the diabetic heart.In addition,insulin levels and other trophic factors change significantly to maintain the ionic channel expression in diabetic patients.There are many diagnostic tools and management options for DCM,but it is difficult to detect its development and to effectively prevent its progress.In this review,diabetes-associated alterations in voltage-sensitive cardiac ion channels are comprehensively assessed to understand their potential role in the pathophysiology and pathogenesis of DCM.展开更多
MXene has given great promises to superca-pacitor electrode material due to its high conductivity and redox properties.However,the self-agglomeration of the MXene lamella will reduce its contact area with the elec-tro...MXene has given great promises to superca-pacitor electrode material due to its high conductivity and redox properties.However,the self-agglomeration of the MXene lamella will reduce its contact area with the elec-trolyte and generate a tortuous transportation pathway of the electrolyte ions,thereby reducing its capacitive per-formance and rate capability.In this work,we engineered the electrolyte ion channels by adjusting the MXene lamella size and inserting holey graphene(HG)nanosheets into the interlayer of the MXene flakes.The developed MXene/HG electrode can not only avoid the self-restack-ing of MXene but also provide unimpeded ion transport channels.As a result,the supercapacitive and rate perfor-mances of the small MXene lamella-based MXene/HG(S-MXene/HG)supercapacitor are prominently ameliorated.By adjusting the content of HG,the S-MXene/HG0.05 electrode exhibits excellent gravimetric capacitance of 446 F·g^(-1)and a rate capability of 77.5%.The S-MXene/HG0.05-based symmetric supercapacitor provides an impressive energy density of 14.84 Wh·kg^(-1)with excellent cyclic stability of 96%capacitance retention after 10,000 cycles.This demonstration of the engineering of the ion channels shows great potential in two-dimensional mate-rial-based supercapacitor electrodes.展开更多
Activation of acid-sensing ion channels （ASICs） plays an important role in neuroinflammation. Macrophage recruitment to the sites of inflammation is an essential step in host defense. ASIC1 and ASIC3 have been repor...Activation of acid-sensing ion channels （ASICs） plays an important role in neuroinflammation. Macrophage recruitment to the sites of inflammation is an essential step in host defense. ASIC1 and ASIC3 have been reported to mediate the endocytosis and maturation of bone marrow derived macrophages. However, the expression and inflammation-related functions of ASICs in RAW 264.7 cells, another common macrophage, are still elusive. In the present study, we first demonstrated the presence of ASIC 1, ASIC2a and ASIC3 in RAW 264.7 macrophage cell line by using reverse transcriptase polymerase chain reaction （RT-PCR）, Western blotting and immunofluorescence experiments. The non-specific ASICs inhibitor amiloride and specific homomeric ASICla blocker PcTxl reduced the production of iNOS and COX-2 by LPS-induced activating RAW 264.7 cells. Furthermore, not only amiloride but also PcTxl inhibited the migration and LPS-induced apoptosis of RAW 264.7 cells. Taken together, our findings suggest that ASICs promote the inflammatory response and apoptosis of RAW 264.7 cells, and ASICs may serve as a potential novel target for immunological disease therapy.展开更多
Ion channels are attractive targets for drug discovery as an increasing number of new ion channel targets have been uncovered in diseases, such as pain, cardiovascular disease, and neurological disorders. Despite thei...Ion channels are attractive targets for drug discovery as an increasing number of new ion channel targets have been uncovered in diseases, such as pain, cardiovascular disease, and neurological disorders. Despite their relevance in diseases and the variety of physiological functions they are involved in, ion channels still remain underexploited as drug targets. This, to a large extent, is attributed to the absence of screening technologies that ensure both the quality and the throughput of data. However, an increasing number of assays and technologies have evolved rapidly in the past decades. In this review, we summarized the currently available high-throughput screening technologies in ion channel drug discovery.展开更多
The locus coeruleus(LC) is one of the essential chemoregulatory and sleep–wake(S–W) modulating centers in the brain. LC neurons remain highly active during wakefulness, and some implicitly become silent during rapid...The locus coeruleus(LC) is one of the essential chemoregulatory and sleep–wake(S–W) modulating centers in the brain. LC neurons remain highly active during wakefulness, and some implicitly become silent during rapid eye movement(REM) sleep. LC neurons are also involved in CO_2-dependent modulation of the respiratory drive. Acid-sensing ion channels(ASICs) are highly expressed in some brainstem chemosensory breathing regulatory areas, but their localization and functions in the LC remain unknown. Mild hypercapnia increases the amount of non-REM(NREM) sleep and the number of REM sleep episodes, but whether ASICs in the LC modulate S–W is unclear. Here, we investigated the presence of ASICs in the LC and their role in S–W modulation and the state transition from NREM to REM sleep. Male Wistar rats were surgically prepared for chronic polysomnographic recordings and drug microinjections into the LC. The presence of ASIC-2 and ASIC-3 in the LC was immunohistochemically characterized.Microinjections of amiloride(an ASIC blocker) and APETx2(a blocker of ASIC-2 and-3) into the LC significantly decreased wakefulness and REM sleep, but significantly increased NREM sleep. Mild hypercapnia increased the amount of NREM and the number of REM episodes. However, APETx2 microinjection inhibited this increase in REM frequency. These results suggest that the ASICs of LC neurons modulate S–W, indicating that ASICs could play an important role in vigilance-state transition. A mild increase in CO_2 level during NREM sleep sensed by ASICs could be one of the determinants of state transition from NREM to REM sleep.展开更多
Post-amputation pain causes great sufering to amputees,but still no efective drugs are available due to its elusive mechanisms.Our previous clinical studies found that surgical removal or radiofrequency treatment of t...Post-amputation pain causes great sufering to amputees,but still no efective drugs are available due to its elusive mechanisms.Our previous clinical studies found that surgical removal or radiofrequency treatment of the neuroma at the axotomized nerve stump efectively relieves the phantom pain aficting patients after amputation.This indicated an essential role of the residual nerve stump in the formation of chronic post-amputation pain(CPAP).However,the molecular mechanism by which the residual nerve stump or neuroma is involved and regulates CPAP is still a mystery.In this study,we found that nociceptors expressed the mechanosensitive ion channel TMEM63A and macrophages infltrated into the dorsal root ganglion(DRG)neurons worked synergistically to promote CPAP.Histology and qRT-PCR showed that TMEM63A was mainly expressed in mechanical pain-producing non-peptidergic nociceptors in the DRG,and the expression of TMEM63A increased signifcantly both in the neuroma from amputated patients and the DRG in a mouse model of tibial nerve transfer(TNT).Behavioral tests showed that the mechanical,heat,and cold sensitivity were not afected in the Tmem63a-/-mice in the naïve state,suggesting the basal pain was not afected.In the infammatory and post-amputation state,the mechanical allodynia but not the heat hyperalgesia or cold allodynia was signifcantly decreased in Tmem63a-/-mice.Further study showed that there was severe neuronal injury and macrophage infltration in the DRG,tibial nerve,residual stump,and the neuromalike structure of the TNT mouse model,Consistent with this,expression of the pro-infammatory cytokines TNFα,IL-6,and IL-1βall increased dramatically in the DRG.Interestingly,the deletion of Tmem63a signifcantly reduced the macrophage infltration in the DRG but not in the tibial nerve stump.Furthermore,the ablation of macrophages signifcantly reduced both the expression of Tmem63a and the mechanical allodynia in the TNT mouse model,indicating an interaction between nociceptors and macrophages,and that these two factors gang up together to regulate the formation of CPAP.This provides a new insight into the mechanisms underlying CPAP and potential drug targets its treatment.展开更多
Ion channels,as membrane proteins,are the sensors of the cell.They act as the first line of communication with the world beyond the plasma membrane and transduce changes in the external and internal environments into ...Ion channels,as membrane proteins,are the sensors of the cell.They act as the first line of communication with the world beyond the plasma membrane and transduce changes in the external and internal environments into unique electrical signals to shape the responses of excitable cells.Because of their importance in cellular communication,ion channels have been intensively studied at the structural and functional levels.Here,we summarize the diverse approaches,including molecular and cellular,chemical,optical,biophysical,and computational,used to probe the structural and functional rearrangements that occur during channel activation（or sensitization）,inactivation（or desensitization）,and various forms of modulation.The emerging insights into the structure and function of ion channels by multidisciplinary approaches allow the development of new pharmacotherapies as well as new tools useful in controlling cellular activity.展开更多
In the retina, pH fluctuations may play an important role in adapting retinal responses to different light intensities and are involved in the fine tuning of visual perception. Acidosis occurs in the subretinal space ...In the retina, pH fluctuations may play an important role in adapting retinal responses to different light intensities and are involved in the fine tuning of visual perception. Acidosis occurs in the subretinal space （SRS） under pathological conditions such as age-related macular degeneration （AMD）. Although it is well known that many transporters in the retinal pigment epithelium （RPE） cells can maintain pH homeostasis efficiently, other receptors in RPE may also be involved in sensing acidosis, such as acid-sensing ion channels （ASICs）. In this study, we investigated whether ASICla was ex- pressed in the RPE cells and whether it was involved in the function of these cells. Real-time RT-PCR and Western blotting were used to analyze the ASICla expression in ARPE-19 cells during oxidative stress induced by hydrogen peroxide （H202）. Furthermore, inhibition or over-expression of ASICla in RPE cells was obtained using inhibitors （amiloride and PCTxl） or by the transfection of cDNA encod- ing hASICla. Cell viability was determined by using the MTT assay. The real-time RT-PCR and West- ern blotting results showed that both the mRNA and protein of ASICla were expressed in RPE cells. In- hibition of ASICs by amiloride in normal RPE cells resulted in cell death, indicating that ASICs play an important physiological role in RPE cells. Furthermore, over-expression of ASICla in RPE cells pro- longed cell survival under oxidative stress induced by H2O2. In conclusion, ASICla is functionally expressed in RPE cells and may play an important role in the physiological function of RPE cells by pro-tecting them from oxidative stress.展开更多
Ischemic postconditioning renders brain tissue tolerant to brain ischemia,thereby alleviating ischemic brain injury.However,the exact mechanism of action is still unclear.In this study,a rat model of global brain isch...Ischemic postconditioning renders brain tissue tolerant to brain ischemia,thereby alleviating ischemic brain injury.However,the exact mechanism of action is still unclear.In this study,a rat model of global brain ischemia was subjected to ischemic postconditioning treatment using the vessel occlusion method.After 2 hours of ischemia,the bilateral common carotid arteries were blocked immediately for 10 seconds and then perfused for 10 seconds.This procedure was repeated six times.Ischemic postconditioning was found to mitigate hippocampal CA1 neuronal damage in rats with brain ischemia,and up-regulate acid-sensing ion channel 2a expression at the m RNA and protein level.These findings suggest that ischemic postconditioning up-regulates acid-sensing ion channel 2a expression in the rat hippocampus after global brain ischemia,which promotes neuronal tolerance to ischemic brain injury.展开更多
OBJECTIVE:To investigate the impact of electro-acupuncture at the Neiguan(PC 6) acupoint on protein and RNA expression of acid-sensing ion channel 2(ASIC2) and ASIC3 in myocardial ischemia rats.METHODS:Fifty male Spra...OBJECTIVE:To investigate the impact of electro-acupuncture at the Neiguan(PC 6) acupoint on protein and RNA expression of acid-sensing ion channel 2(ASIC2) and ASIC3 in myocardial ischemia rats.METHODS:Fifty male Sprague-Dawley rats were used,weighing(230 ± 50) g.The rats were randomized into a normal group A,model group B,Neiguan(PC 6) group C,Lieque(LU 7) group D,and A-shi points group E.There were 10 rats in each group.Rats were continuously administered 85 mg/kg intravenous isoproterenol daily to establish the model.Successfully modeled rats in groups C,D,and E were given electro-acupuncture treatment.Each group of rats was sacrificed with chloral hydrate(1 mL/100 g) intraperitoneal injection.The left ventricular myocardium was extracted and placed at- 70 ℃ until use.Western blot analysis and real-time PCR were performed to assay protein and RNA expressions of ASIC2 and ASIC3,respectively.Fold changes in RNA expression were quantified with the 2~^(-△△Ct) method.Blood samples were drawn from the aorta abdominalis and tested for creatine kinase-MB(CK-MB) and lactate dehydrogenase(LDH) levels using enzyme-linked immunosorbent assay.RESULTS:Myocardial ischemia rats given electro-acupuncture at the Neiguan(PC 6) acupoint had significantly lower protein and RNA expression of ASIC2 and ASIC3,and CK-MB and LDH levels,compared with model rats(P < 0.01).CONCLUSION:Electro-acupuncture at the Neiguan(PC 6) acupoint can not only decrease the protein and RNA expression of ASIC2 and ASIC3,but also inhibit the opening of ASICs and reduce the cardiomyocyte damage in myocardial ischemia rats.展开更多
Capacitation and acrosome reaction are important prerequisites of the fertilization process. Capacitation is a highlycomplex phenomenon occurring in the female genital tract, rendering the spermatozoa capable of bindi...Capacitation and acrosome reaction are important prerequisites of the fertilization process. Capacitation is a highlycomplex phenomenon occurring in the female genital tract, rendering the spermatozoa capable of binding and fusionwith the oocyte. During capacitation various biochemical and biophysical changes occur in the spermatozoa and thespermatozoal membranes. Ions and ion channels also play important roles in governing the process of capacitation bychanging the fluxes of different ions which in turn controls various characteristics of capacitated spermatozoa. Alongwith the mobilization of ions the generation of free radicals and efflux of cholesterol also plays an important role in thecapacitation state of the spermatozoa. The generation of free radical and efflux of cholesterol change the mechano-dynamic properties of the membrane by oxidation of the polyunsaturated lipids and by generating the cholesterol freepatches. The process of capacitation renders the spermatozoa responsive to the inducers of the acrosome reaction. Theglycoprotein zona pellucida 3 (ZP3) of the egg coat zona pellucida is the potent physiological stimulator of the acro-some reaction; progesterone, a major compoent of the follicular fluid, is also an induce of the acrosome reaction.The inducers of the acrosome reaction cause the activation of the various ion-channels leading to high influxes of calci-um, sodium and bicarbonate. The efflux of cholesterol during the process of capacitation alters the permeablity of themembrane to the ions and generate areas which are prone to fusion and vesculation process during the acrosome reac-tion. Ths review focuses mainly on effects of the ion and ion-channels, free radicals, and membrane fluidity changesduring the process of capacitation and acrosome reaction. (Asian J Androl 1999 Sep; 1: 95-107)展开更多
基金supported by ANID-FONDECYT 1200908(to JF),ANID-FONDECYT 1211082 and 1250856(to GEY)by the Millennium Nucleus for the Study of Pain NCN19_038(Mi Nu SPain)(to GEY)funded by the ANID scholarship 21201176。
文摘Numerous pathological states of the nervous system involve alterations in neuronal excitability and synaptic dysfunction,which depend on the function of ion channels.Due to their critical involvement in health and disease,the search for new compounds that modulate these proteins is still relevant.Traditional medicine has long been a rich source of neuroactive compounds.For example,the indigenous Mapuche people have used the leaves and bark of the Drimys winteri tree for centuries to treat various diseases.Consequently,several studies have investigated the biological effects of compounds in Drimys winteri,highlighting sesquiterpenes such asα-humulene,drimenin,polygodial,andα-,β-,γ-eudesmol.However,there is currently no literature review focusing on the ability of these sesquiterpenes to modulate ion channels.This review summarizes the current knowledge about neuroactive compounds found in Drimys winteri,with special emphasis on their direct actions on neuronal ion channels.Several Drimys winteri sesquiterpenes modulate a diverse array of neuronal ion channels,including transient receptor potential channels,gamma-aminobutyric acid A receptors,nicotinic acetylcholine receptors,and voltage-dependent Ca^(2+)and Na^(+)channels.Interestingly,the modulation of these molecular targets by Drimys winteri sesquiterpenes correlates with their therapeutic actions.The promiscuous pharmacological profile of Drimys winteri sesquiterpenes suggests they modulate multiple protein targets in vivo,making them potentially useful for treating complex,multifactorial diseases.Further studies at the molecular level may aid in developing multitargeted drugs with enhanced therapeutic effects.
基金supported by the National Science Basic Research Program of Shaanxi(Grant No.2023-JC-QN-0087)。
文摘The ion channel in neurons is the basic component of signal transmission in the nervous system.The ion channel has important effects on the potential of neuron release and dynamic behavior in neural networks.Ion channels control the flow of ions into and out of the cell membrane to form an ion current,which makes the excitable membrane produce special potential changes and become the basis of nerve and muscle activity.The blockage of ion channels has a significant effect on the dynamics of neurons and networks.Therefore,it is very meaningful to study the influence of ion channels on neuronal dynamics.In this work,a hybrid ion channel is designed by connecting a charge-controlled memristor(CCM)with an inductor in series,and a magnetic flux-controlled memristor(MFCM),capacitor,and nonlinear resistor are connected in parallel with the mixed ion channel to obtain the memristor neural circuit.Furthermore,the oscillator model with a hybrid ion channel and its energy function are calculated,and a map neuron is obtained by linearizing the neuron oscillator model.In addition,an adaptive regulation method is designed to explore the adaptive regulation of energy on the dynamic behaviors of the map neuron.The results show that the dynamics of a map neuron with a hybrid ion channel can be controlled by parameters and external magnetic fields.This study is also used to research synchronization between map neurons and collective behaviors in the map neurons network.
基金supported by research grants from the National Key Research and Development Program of China(No.2022YFB3803300)the Natural Science Foundation of China(Nos.52173235 and 62074022)+2 种基金the Venture&Innovation Support Program for Chongqing Overseas Returnees(No.CX2021018)the Youth Talent Support Program of Chongqing(No.CQYC2021059206)the Program of Graduate Education and Teaching in Chongqing(No.yjg223016).
文摘The inherent safety,high theoretical specific capacity and low raw material cost of aqueous batteries make them potential candidates in large-scale energy storage.However,uncontrolled dendrite growth,parasitic reactions and sluggish mass transfer on the anode-electrolyte interface are the main challenges restricting the application prospect of aqueous zinc-ion batteries.In general,eukaryotic cells utilize specific ion channels to achieve ion migration with the merits of low energy consumption and rapid speed.Herein,migrating the concept of ion channels to aqueous batteries,a crown species encapsulated zeolitic imidazolate framework(ZIF)interfacial layer(denoted as ZIF@Crown)was ex situ decorated onto the Zn anode.Similar to biological ion channels,the ZIF@Crown layer can homogenize the distribution of Zn^(2+)on the anode,accelerate the desolvation of hydrated Zn^(2+)and reduce the energy barrier for Zn^(2+)deposition,which were verified by theoretical calculations and experimental characterizations.Benefiting from these efficacious modulation mechanisms,the Zn@ZIF@Crown symmetrical cell could achieve a long calendar life of over 1900 h and the Zn@ZIF@Crown||Cu also sustained 600 cycles with a high Coulombic efficiency(97%).Furthermore,the full cells containing ZIF@Crown layer exhibit desirable electrochemical performance.This work provides an innovative avenue toward the optimization of aqueous batteries via bionic interfacial engineering.
文摘The authors used suspension cells of Populus euphratica to isolate protoplast in the present study. Protoplasts were successfully obtained after 4 hours incubation in enzyme solution containing 1 0% cellulase “onozuka” R\|10, 0\^01% pectolyase Y\|23,0\^15% macerozyme R\|10 and 0\^1% hemicellulase at 25℃. Outward and inward single channels in plasma membrane were observed using cell\|attached recording of patch\|clamp technique. In this study, single channel records showed that more than one species of channel were obtained. These attempts in protoplast isolation and ion channel recording offers the opportunity to characterize cellular mechanisms of salt tolerance in tree species.
基金This work was supported by the Provincial Key Projects for Scientifical and Technological Research of Zhejiang Province (No. 2006C12058)National Natural Science Foundation of China (No. 30571335) and a Grant-in-Aid for Innovative Training of Doctoral Students in JIangsu Province,China.
文摘Cyclic nucleotide-gated ion channels （CNGs） are distributed most widely in the neuronal cell. Great progress has been made in molecular mechanisms of CNG channel gating in the recent years. Results of many experiments have indicated that the stoichiometry and assembly of CNG channels affect their property and gating. Experiments of CNG mutants and analyses of cys- teine accessibilities show that cyclic nucleotide-binding domains （CNBD） bind cyclic nucleotides and subsequently conformational changes occurred followed by the concerted or cooperative conformational change of all four subunits during CNG gating. In order to provide theoretical assistances for further investigation on CNG channels, especially regarding the disease pathogenesis of ion channels, this paper reviews the latest progress on mechanisms of CNG channels, functions of subunits, processes of subunit assembly, and conformational changes of subunit regions during gating.
文摘Objective To re-confirm and characterize the biophysical and pharmacological properties of endogenously expressed human acid-sensing ion channel 1a （hASIC1a） current in HEK293 cells with a modified perfusion methods. Methods With cell floating method, which is separating the cultured cell from coverslip and putting the cell in front of perfusion tubing, whole cell patch clamp technique was used to record hASICla currents evoked by low pH external solution. Results Using cell floating method, the amplitude of hASICla currents activated by pH 5.0 in HEK293 cells is twice as large as that by the conventional method where the cells remain attached to coverslip. The time to reach peak at two different recording conditions is （21±5） ms and （270±25） ms, respectively. Inactivation time constants are （496±23） ms and （2284±120） ms, respectively. The cell floating method significantly increases the amiloride potency of block on hASIC 1 a [IC50 is （3.4± 1.1 ） μmol/L and （2.4± 0.9） μmol/L, respectively]. Both recording methods have similar pH activation ECs0 （6.6±0.6, 6.6±0.7, respectively）. Conclusion ASICs channel activation requires fast exchange of extracellular solution with the different pH values. With cell floating method, the presence of hASIC la current was re-confirmed and the biophysical and pharmacological properties of hASIC la channel in HEK293 cells was precisely characterized. This method could be used to study all ASICs and other ligand-gated channels that require fast extracellular solution exchange.
基金supported by the National Natural Science Foundation of China (81571273,81571274,81501124,81271434,and 81301107)Omics-based precision medicine of epilepsy being entrusted by Key Research Project of the Ministry of Science and Technology of China (2016YFC0904400)+5 种基金the Natural Science Foundation of Guangdong Province,China (2014A030313489)Science and Technology Planning Projects of Guangdong Province,China (2012B031800404 and 2013B051000084)the Department of Education of Guangdong Province,China (2013CXZDA022,2013KJCX0156,and 2012KJCX009)the Foundation for High-level Talents in Higher Education of Guangdong Province,China (2013-167)Yangcheng Scholar Research Projects of Guangzhou Municipal College (12A016S and 12A017G)Science and Technology Projects of Guangzhou,Guangdong Province,China (2014J4100069,201508020011,201604020161,and 201607010002)
文摘Ion channels are crucial in the generation and modulation of excitability in the nervous system and have been implicated in human epilepsy. Forty-one epilepsyassociated ion channel genes and their mutations are systematically reviewed. In this paper, we analyzed the genotypes, functional alterations（funotypes）, and phenotypes of these mutations. Eleven genes featured loss-offunction mutations and six had gain-of-function mutations.Nine genes displayed diversified funotypes, among which a distinct funotype-phenotype correlation was found in SCN1A. These data suggest that the funotype is an essential consideration in evaluating the pathogenicity of mutations and a distinct funotype or funotype-phenotype correlation helps to define the pathogenic potential of a gene.
文摘Sexually reproducing animals require an orchestrated communication between spermatozoa and the egg to generate a new individual. Capacitation, a maturational complex phenomenon that occurs in the female reproductive tract, renders spermatozoa capable of binding and fusing with the oocyte, and it is a requirement for mammalian fertilization. Capacitation encompasses plasma membrane reorganization, ion permeability regulation, cholesterol loss and changes in the phosphorylation state of many proteins. Novel tools to study sperm ion channels, image intracellular ionic changes and proteins with better spatial and temporal resolution, are unraveling how modifications in sperm ion transport and phosphorylation states lead to capacitation. Recent evidence indicates that two parallel pathways regulate phosphorylation events leading to capacitation, one of them requiring activation of protein kinase A and the second one involving inactivation of ser/thr phosphatases. This review examines the involvement of ion transporters and phosphorylation signaling processes needed for spermatozoa to achieve capacitation. Understanding the molecular mechanisms leading to fertilization is central for societies to deal with rising male infertility rates, to develop safe male gamete-based contraceptives and to preserve biodiversity through better assisted fertilization strategies.
基金Supported by Sichuan Science and Technology Program,No.2018SZ0386。
文摘Neuropathic pain(NPP)is a kind of pain caused by disease or damage impacting the somatosensory system.Ion channel drugs are the main treatment for NPP;however,their irregular usage leads to unsatisfactory pain relief.To regulate the treatment of NPP with ion channel drugs in clinical practice,the Chinese Association for the Study of Pain organized first-line pain management experts from China to write an expert consensus as the reference for the use of ion channels drugs.Here,we reviewed the mechanism and characteristics of sodium and calcium channel drugs,and developed recommendations for the therapeutic principles and clinical practice for carbamazepine,oxcarbazepine,lidocaine,bulleyaconitine A,pregabalin,and gabapentin.We hope this guideline provides guidance to clinicians and patients on the use of ion channel drugs for the management of NPP.
文摘Diabetes mellitus affects the heart through various mechanisms such as microvascular defects,metabolic abnormalities,autonomic dysfunction and incompatible immune response.Furthermore,it can also cause functional and structural changes in the myocardium by a disease known as diabetic cardiomyopathy(DCM)in the absence of coronary artery disease.As DCM progresses it causes electrical remodeling of the heart,left ventricular dysfunction and heart failure.Electrophysiological changes in the diabetic heart contribute significantly to the incidence of arrhythmias and sudden cardiac death in diabetes mellitus patients.In recent studies,significant changes in repolarizing K+currents,Na+currents and L-type Ca^(2+)currents along with impaired Ca^(2+ )homeostasis and defective contractile function have been identified in the diabetic heart.In addition,insulin levels and other trophic factors change significantly to maintain the ionic channel expression in diabetic patients.There are many diagnostic tools and management options for DCM,but it is difficult to detect its development and to effectively prevent its progress.In this review,diabetes-associated alterations in voltage-sensitive cardiac ion channels are comprehensively assessed to understand their potential role in the pathophysiology and pathogenesis of DCM.
基金financially supported by the National Key R&D Program of China (No.2017YFA0304203)the National Natural Science Foundation of China (Nos.21805174 and 51902190)+5 种基金the Key Research and Development Program of Shanxi Province for International Cooperation (No.201803D421082)the Scientific and Technological Innovation Programs of Higher Education Institutions in Shanxi (Nos.2019L0013 and 2019L0018)Shanxi Scholarship Council of China (No.2021-004)the Program of Introducing Talents of Discipline to Universities (No.D18001)the Changjiang Scholars and Innovative Research Team at the University of Ministry of Education of China (No.IRT_17R70)the Fund for Shanxi “1331 Project”
文摘MXene has given great promises to superca-pacitor electrode material due to its high conductivity and redox properties.However,the self-agglomeration of the MXene lamella will reduce its contact area with the elec-trolyte and generate a tortuous transportation pathway of the electrolyte ions,thereby reducing its capacitive per-formance and rate capability.In this work,we engineered the electrolyte ion channels by adjusting the MXene lamella size and inserting holey graphene(HG)nanosheets into the interlayer of the MXene flakes.The developed MXene/HG electrode can not only avoid the self-restack-ing of MXene but also provide unimpeded ion transport channels.As a result,the supercapacitive and rate perfor-mances of the small MXene lamella-based MXene/HG(S-MXene/HG)supercapacitor are prominently ameliorated.By adjusting the content of HG,the S-MXene/HG0.05 electrode exhibits excellent gravimetric capacitance of 446 F·g^(-1)and a rate capability of 77.5%.The S-MXene/HG0.05-based symmetric supercapacitor provides an impressive energy density of 14.84 Wh·kg^(-1)with excellent cyclic stability of 96%capacitance retention after 10,000 cycles.This demonstration of the engineering of the ion channels shows great potential in two-dimensional mate-rial-based supercapacitor electrodes.
基金This work was supported by grants from the National Natural science Foundation of China （No. 81473199）, and the Fundamental Research Funds for the Central Universities （No, 015TS 125）.
文摘Activation of acid-sensing ion channels （ASICs） plays an important role in neuroinflammation. Macrophage recruitment to the sites of inflammation is an essential step in host defense. ASIC1 and ASIC3 have been reported to mediate the endocytosis and maturation of bone marrow derived macrophages. However, the expression and inflammation-related functions of ASICs in RAW 264.7 cells, another common macrophage, are still elusive. In the present study, we first demonstrated the presence of ASIC 1, ASIC2a and ASIC3 in RAW 264.7 macrophage cell line by using reverse transcriptase polymerase chain reaction （RT-PCR）, Western blotting and immunofluorescence experiments. The non-specific ASICs inhibitor amiloride and specific homomeric ASICla blocker PcTxl reduced the production of iNOS and COX-2 by LPS-induced activating RAW 264.7 cells. Furthermore, not only amiloride but also PcTxl inhibited the migration and LPS-induced apoptosis of RAW 264.7 cells. Taken together, our findings suggest that ASICs promote the inflammatory response and apoptosis of RAW 264.7 cells, and ASICs may serve as a potential novel target for immunological disease therapy.
基金supported by the State Key Laboratory of Natural and Biomimetic Drugs, Peking University。
文摘Ion channels are attractive targets for drug discovery as an increasing number of new ion channel targets have been uncovered in diseases, such as pain, cardiovascular disease, and neurological disorders. Despite their relevance in diseases and the variety of physiological functions they are involved in, ion channels still remain underexploited as drug targets. This, to a large extent, is attributed to the absence of screening technologies that ensure both the quality and the throughput of data. However, an increasing number of assays and technologies have evolved rapidly in the past decades. In this review, we summarized the currently available high-throughput screening technologies in ion channel drug discovery.
基金supported by the Department of Science and Technology-Cognitive Science Initiative project funded to Sushil K Jhasupport from Department of Biotechnology (DBT), Department of Science and Technology(PURSE), Universities for Potential of Excellence (UPOE Ⅱ) and University Grants Commission-Special Assistance Programme)JNU funds to Sushil K Jha。
文摘The locus coeruleus(LC) is one of the essential chemoregulatory and sleep–wake(S–W) modulating centers in the brain. LC neurons remain highly active during wakefulness, and some implicitly become silent during rapid eye movement(REM) sleep. LC neurons are also involved in CO_2-dependent modulation of the respiratory drive. Acid-sensing ion channels(ASICs) are highly expressed in some brainstem chemosensory breathing regulatory areas, but their localization and functions in the LC remain unknown. Mild hypercapnia increases the amount of non-REM(NREM) sleep and the number of REM sleep episodes, but whether ASICs in the LC modulate S–W is unclear. Here, we investigated the presence of ASICs in the LC and their role in S–W modulation and the state transition from NREM to REM sleep. Male Wistar rats were surgically prepared for chronic polysomnographic recordings and drug microinjections into the LC. The presence of ASIC-2 and ASIC-3 in the LC was immunohistochemically characterized.Microinjections of amiloride(an ASIC blocker) and APETx2(a blocker of ASIC-2 and-3) into the LC significantly decreased wakefulness and REM sleep, but significantly increased NREM sleep. Mild hypercapnia increased the amount of NREM and the number of REM episodes. However, APETx2 microinjection inhibited this increase in REM frequency. These results suggest that the ASICs of LC neurons modulate S–W, indicating that ASICs could play an important role in vigilance-state transition. A mild increase in CO_2 level during NREM sleep sensed by ASICs could be one of the determinants of state transition from NREM to REM sleep.
基金supported by grants from the Ministry of Science and Technology of China(2021ZD0203201)the National Natural Science Foundation of China(81971034,81672237)+3 种基金The Innovative Research Team of High-level Local Universities in Shanghai,Shanghai Pujiang Program(19PJ1401700)the Natural Science Foundation of Shanghai Municipality(22ZR1413800)The Program for Professor of Special Appointment(Eastern Scholar)at Shanghai Institutions of Higher Learning,Shanghai Municipal Science and Technology Major Project(2018SHZDZX01)ZJ Lab,and Shanghai Center for Brain Science and Brain-Inspired Technology,Innovation Team and Talents Cultivation Program of the National Administration of Traditional Chinese Medicine(ZYYCXTD-C-202008).
文摘Post-amputation pain causes great sufering to amputees,but still no efective drugs are available due to its elusive mechanisms.Our previous clinical studies found that surgical removal or radiofrequency treatment of the neuroma at the axotomized nerve stump efectively relieves the phantom pain aficting patients after amputation.This indicated an essential role of the residual nerve stump in the formation of chronic post-amputation pain(CPAP).However,the molecular mechanism by which the residual nerve stump or neuroma is involved and regulates CPAP is still a mystery.In this study,we found that nociceptors expressed the mechanosensitive ion channel TMEM63A and macrophages infltrated into the dorsal root ganglion(DRG)neurons worked synergistically to promote CPAP.Histology and qRT-PCR showed that TMEM63A was mainly expressed in mechanical pain-producing non-peptidergic nociceptors in the DRG,and the expression of TMEM63A increased signifcantly both in the neuroma from amputated patients and the DRG in a mouse model of tibial nerve transfer(TNT).Behavioral tests showed that the mechanical,heat,and cold sensitivity were not afected in the Tmem63a-/-mice in the naïve state,suggesting the basal pain was not afected.In the infammatory and post-amputation state,the mechanical allodynia but not the heat hyperalgesia or cold allodynia was signifcantly decreased in Tmem63a-/-mice.Further study showed that there was severe neuronal injury and macrophage infltration in the DRG,tibial nerve,residual stump,and the neuromalike structure of the TNT mouse model,Consistent with this,expression of the pro-infammatory cytokines TNFα,IL-6,and IL-1βall increased dramatically in the DRG.Interestingly,the deletion of Tmem63a signifcantly reduced the macrophage infltration in the DRG but not in the tibial nerve stump.Furthermore,the ablation of macrophages signifcantly reduced both the expression of Tmem63a and the mechanical allodynia in the TNT mouse model,indicating an interaction between nociceptors and macrophages,and that these two factors gang up together to regulate the formation of CPAP.This provides a new insight into the mechanisms underlying CPAP and potential drug targets its treatment.
基金supported by grants from the National Natural Science Foundation of China(91132303,30830035)the National Basic Research Development Program of China (2011CBA00408)the China Postdoctoral Science Foundation(2012M511105)
文摘Ion channels,as membrane proteins,are the sensors of the cell.They act as the first line of communication with the world beyond the plasma membrane and transduce changes in the external and internal environments into unique electrical signals to shape the responses of excitable cells.Because of their importance in cellular communication,ion channels have been intensively studied at the structural and functional levels.Here,we summarize the diverse approaches,including molecular and cellular,chemical,optical,biophysical,and computational,used to probe the structural and functional rearrangements that occur during channel activation（or sensitization）,inactivation（or desensitization）,and various forms of modulation.The emerging insights into the structure and function of ion channels by multidisciplinary approaches allow the development of new pharmacotherapies as well as new tools useful in controlling cellular activity.
基金supported by the National Natural Science Foundation of China (No. 81200681)
文摘In the retina, pH fluctuations may play an important role in adapting retinal responses to different light intensities and are involved in the fine tuning of visual perception. Acidosis occurs in the subretinal space （SRS） under pathological conditions such as age-related macular degeneration （AMD）. Although it is well known that many transporters in the retinal pigment epithelium （RPE） cells can maintain pH homeostasis efficiently, other receptors in RPE may also be involved in sensing acidosis, such as acid-sensing ion channels （ASICs）. In this study, we investigated whether ASICla was ex- pressed in the RPE cells and whether it was involved in the function of these cells. Real-time RT-PCR and Western blotting were used to analyze the ASICla expression in ARPE-19 cells during oxidative stress induced by hydrogen peroxide （H202）. Furthermore, inhibition or over-expression of ASICla in RPE cells was obtained using inhibitors （amiloride and PCTxl） or by the transfection of cDNA encod- ing hASICla. Cell viability was determined by using the MTT assay. The real-time RT-PCR and West- ern blotting results showed that both the mRNA and protein of ASICla were expressed in RPE cells. In- hibition of ASICs by amiloride in normal RPE cells resulted in cell death, indicating that ASICs play an important physiological role in RPE cells. Furthermore, over-expression of ASICla in RPE cells pro- longed cell survival under oxidative stress induced by H2O2. In conclusion, ASICla is functionally expressed in RPE cells and may play an important role in the physiological function of RPE cells by pro-tecting them from oxidative stress.
文摘Ischemic postconditioning renders brain tissue tolerant to brain ischemia,thereby alleviating ischemic brain injury.However,the exact mechanism of action is still unclear.In this study,a rat model of global brain ischemia was subjected to ischemic postconditioning treatment using the vessel occlusion method.After 2 hours of ischemia,the bilateral common carotid arteries were blocked immediately for 10 seconds and then perfused for 10 seconds.This procedure was repeated six times.Ischemic postconditioning was found to mitigate hippocampal CA1 neuronal damage in rats with brain ischemia,and up-regulate acid-sensing ion channel 2a expression at the m RNA and protein level.These findings suggest that ischemic postconditioning up-regulates acid-sensing ion channel 2a expression in the rat hippocampus after global brain ischemia,which promotes neuronal tolerance to ischemic brain injury.
基金Supported by National Essence Basic Research and Development 973 Program(the Effects of Meridian Specific Target Organ Response to Biological Basic Research,No.2012CB518503)
文摘OBJECTIVE:To investigate the impact of electro-acupuncture at the Neiguan(PC 6) acupoint on protein and RNA expression of acid-sensing ion channel 2(ASIC2) and ASIC3 in myocardial ischemia rats.METHODS:Fifty male Sprague-Dawley rats were used,weighing(230 ± 50) g.The rats were randomized into a normal group A,model group B,Neiguan(PC 6) group C,Lieque(LU 7) group D,and A-shi points group E.There were 10 rats in each group.Rats were continuously administered 85 mg/kg intravenous isoproterenol daily to establish the model.Successfully modeled rats in groups C,D,and E were given electro-acupuncture treatment.Each group of rats was sacrificed with chloral hydrate(1 mL/100 g) intraperitoneal injection.The left ventricular myocardium was extracted and placed at- 70 ℃ until use.Western blot analysis and real-time PCR were performed to assay protein and RNA expressions of ASIC2 and ASIC3,respectively.Fold changes in RNA expression were quantified with the 2~^(-△△Ct) method.Blood samples were drawn from the aorta abdominalis and tested for creatine kinase-MB(CK-MB) and lactate dehydrogenase(LDH) levels using enzyme-linked immunosorbent assay.RESULTS:Myocardial ischemia rats given electro-acupuncture at the Neiguan(PC 6) acupoint had significantly lower protein and RNA expression of ASIC2 and ASIC3,and CK-MB and LDH levels,compared with model rats(P < 0.01).CONCLUSION:Electro-acupuncture at the Neiguan(PC 6) acupoint can not only decrease the protein and RNA expression of ASIC2 and ASIC3,but also inhibit the opening of ASICs and reduce the cardiomyocyte damage in myocardial ischemia rats.
文摘Capacitation and acrosome reaction are important prerequisites of the fertilization process. Capacitation is a highlycomplex phenomenon occurring in the female genital tract, rendering the spermatozoa capable of binding and fusionwith the oocyte. During capacitation various biochemical and biophysical changes occur in the spermatozoa and thespermatozoal membranes. Ions and ion channels also play important roles in governing the process of capacitation bychanging the fluxes of different ions which in turn controls various characteristics of capacitated spermatozoa. Alongwith the mobilization of ions the generation of free radicals and efflux of cholesterol also plays an important role in thecapacitation state of the spermatozoa. The generation of free radical and efflux of cholesterol change the mechano-dynamic properties of the membrane by oxidation of the polyunsaturated lipids and by generating the cholesterol freepatches. The process of capacitation renders the spermatozoa responsive to the inducers of the acrosome reaction. Theglycoprotein zona pellucida 3 (ZP3) of the egg coat zona pellucida is the potent physiological stimulator of the acro-some reaction; progesterone, a major compoent of the follicular fluid, is also an induce of the acrosome reaction.The inducers of the acrosome reaction cause the activation of the various ion-channels leading to high influxes of calci-um, sodium and bicarbonate. The efflux of cholesterol during the process of capacitation alters the permeablity of themembrane to the ions and generate areas which are prone to fusion and vesculation process during the acrosome reac-tion. Ths review focuses mainly on effects of the ion and ion-channels, free radicals, and membrane fluidity changesduring the process of capacitation and acrosome reaction. (Asian J Androl 1999 Sep; 1: 95-107)
