To explore eutrophication and algal bloom mechanisms in channel type reservoirs, a novel enclosure experiment was conducted by changing light intensity （LI） in the Daning River of the Three Gorges Reservoir （TGR）....To explore eutrophication and algal bloom mechanisms in channel type reservoirs, a novel enclosure experiment was conducted by changing light intensity （LI） in the Daning River of the Three Gorges Reservoir （TGR）. Square enclosures （side 5.0 m） were covered on the surface with shading materials of different thickness, and with their bases open to the river. Changes and characteristics of the main eutrophication factors under the same water quality and hydrodynamic conditions but different LI were evaluated. All experimental water samples were neutral and alkalescent, with high nitrogen and phosphate concentrations, low potassium permanganate index, stable water quality, and different LI. At the same water depth, LI decreased with increasing shade material, while dissolved oxygen and water temperature were both stable. The growth peak of phytoplankton was with light of 345-4390 lux underwater or 558-7450 lux above the water surface, and water temperature of 25.6--26.5℃. Algae were observed in all water samples, accounting for 6 phylum and 57 species, with algal density changing frequently. The results showed that significantly strong or weak light was unfavorable for phytoplankton growth and the function together with suitable temperature and LI and ample sunshine encouraged algal blooms under the same water quality and hydrodynamic conditions. Correlation analysis indicated that algae reduced gradually lengthwise along water depth in the same enclosure while pH became high. The power exponent relationship between chlorophyll a （Chl-a） and LI was found by curve fitting, that is Chl-a = K（LI）n.展开更多
This paper studies the hydrodynamic performance of a channel type planing trimaran. A numerical simulation is carried out based on a RANS-VOF solver to analyze the hydrodynamic performance of the channel type planing ...This paper studies the hydrodynamic performance of a channel type planing trimaran. A numerical simulation is carried out based on a RANS-VOF solver to analyze the hydrodynamic performance of the channel type planing trimaran. A series of hydrodynamic experiments in towing tank were carried out, in which both the running attitude and the resistance performance of the trimaran model were recorded. Some hydrodynamic characteristics of the channel type planning trimaran are shown by the results. Firstly, the resistance declines significantly, with the forward speed across the high-speed resistance peak due to the combined effects of the aerodynamic and hydrodynamic lifts. Secondly, the resistance performance is influenced markedly by the longitudinal positio- ns of centre of the gravity and the displacements. Besides, the pressure distribution on the hull and the two-phase flow in the channel are discussed in the numerical simulations.展开更多
Objective Formaldehyde at high concentrations is a contributor to air pollution. It is also an endogenous metabolic product in cells, and when beyond physiological concentrations, has pathological effects on neurons. ...Objective Formaldehyde at high concentrations is a contributor to air pollution. It is also an endogenous metabolic product in cells, and when beyond physiological concentrations, has pathological effects on neurons. Formaldehyde induces mis-folding and aggregation of neuronal tau protein, hippocampal neuronal apoptosis, cognitive impairment and loss of memory functions, as well as excitation of peripheral nociceptive neurons in cancer pain models. Intracellular calcium （[Ca2＋]i） is an important intracellular messenger, and plays a key role in many pathological processes. The present study aimed to investigate the effect of formaldehyde on [Ca2＋]i and the possible involvement of N-methyl-D-aspartate receptors （NMDARs） and T-type Ca2＋ channels on the cell membrane. Methods Using primary cultured hippocampal neurons as a model, changes of [Ca2＋]i in the presence of formaldehyde at a low concentration were detected by confocal laser scanning microscopy. Results Formaldehyde at 1 mmol/L approximately doubled [Ca2＋]i. （2R）-amino-5-phosphonopentanoate （AP5, 25 μmol/L, an NMDAR antagonist） and mibefradil （MIB, 1 μmol/L, a T-type Ca2＋ channel blocker）, given 5 min after formaldehyde perfusion, each partly inhibited the formaldehyde-induced increase of [Ca：＋]i, and this inhibitory effect was reinforced by combined application of AP5 and MIB. When applied 3 min before formaldehyde perfusion, AP5 （even at 50μmol/L） did not inhibit the formaldehyde-induced increase of [Ca2＋]i, but MIB （1 μmol/L） significantly inhibited this increase by 70%. Conclusion These results suggest that formaldehyde at a low concentration increases [Ca2＋]i in cultured hippocampal neurons; NMDARs and T-type Ca2＋ channels may be involved in this process.展开更多
Intracellular cAMP and Ca^2＋ are involved in the regulation of steroidogenic activity in Leydig cells, which coordinate responses to luteinizing hormone （LH） and human ehorionic gonadotropin （hCG）. However, the i...Intracellular cAMP and Ca^2＋ are involved in the regulation of steroidogenic activity in Leydig cells, which coordinate responses to luteinizing hormone （LH） and human ehorionic gonadotropin （hCG）. However, the identification of Ca^2＋ entry implicated in Leydig cell steroidogenesis is not well defined. The objective of this study was to identify the type of Ca^2＋ channel that affects Leydig cell steroidogenesis. In vitro steroidogenesis in the freshly dissociated Leydig cells of mice was induced by hCG incubation. The effects of mibefradil （a putative T-type Ca^2＋ channel blocker） on steroidogenesis were assessed using reverse transcription （RT）-polymerase chain reaction analysis for the steroidogenic acute regulatory protein （STAR） mRNA expression and testosterone production using radioimmunoassay. In the presence of 1.0 mmol L-1 extracellular Ca^2＋, hCG at 1 to 100 IU noticeably elevated both StAR mRNA level and testosterone secretion （P 〈 0.05）, and the stimulatory effects of hCG were markedly diminished by mibefradil in a dose-dependent manner （P 〈 0.05）. Moreover; the hCG-induced increase in testosterone production was completely removed when external Ca^2＋ was omitted, implying that Ca entry is needed for hCG-induced steroidogenesis. Furthermore, a patch-clamp study revealed the presence of mibefradil-sensitive Ca^24- currents seen at a concentration range that nearly paralleled those inhibiting steroidogenesis. Collectively, Our data provide evidence that hCG-stimulated steroidogenesis is mediated at least in part by Ca^2＋ entry carried out by the T-type Ca^2＋ channel in the Leydig cells of mice.展开更多
Background Atrial fibrillation （AF） is the most common sustained cardiac arrhythmia without effective treatment. AF is associated with atrial conduction disturbances caused by electrical and / or structural remodeli...Background Atrial fibrillation （AF） is the most common sustained cardiac arrhythmia without effective treatment. AF is associated with atrial conduction disturbances caused by electrical and / or structural remodeling. But the role of connexin （Cx） 43 in the regulation of L type calcium channel （LCC） remains unclear. We hypothesized that Cx 43 might co-localize and regulate the L type calcium channel current （ICa, D. Methods Real-time PCR and whole-cell patch clamp were used to detect the expression of LCC lc subunit and the cur rent density of Ica, L, before and after Cx 43 knocking down respectively. The co-localization of Cx 43 with LCC was investigated by co-immunoprecipitation and confocal microscopy. Results Knocking down of Cx43 significantly inhibited the current density of ICa, L through decreasing the gene expression of LCC alc in cul tured atrium-derived myocytes （HL-1 cells）. Cx43 co-localized with LCC eric subunit in atrial myocytes. Conclusions Cx 43 regulates the ICa, L in atrial myoctyes through LCC, representing a potential pathogenic mechanism in atrial arrhythmias.展开更多
A novel groove-type channel enhancement-mode AlGaN/GaN MIS high electron mobility transistor（GTCE-HEMT）with a combined polar and nonpolar AlGaN/GaN heterostucture is presented. The device simulation shows a threshol...A novel groove-type channel enhancement-mode AlGaN/GaN MIS high electron mobility transistor（GTCE-HEMT）with a combined polar and nonpolar AlGaN/GaN heterostucture is presented. The device simulation shows a threshold voltage of 1.24 V, peak transconductance of 182 m S/mm, and subthreshold slope of 85 m V/dec, which are obtained by adjusting the device parameters. Interestingly, it is possible to control the threshold voltage accurately without precisely controlling the etching depth in fabrication by adopting this structure. Besides, the breakdown voltage（VB） is significantly increased by 78% in comparison with the value of the conventional MIS-HEMT. Moreover, the fabrication process of the novel device is entirely compatible with that of the conventional depletion-mode（D-mode） polar AlGaN/GaN HEMT. It presents a promising way to realize the switch application and the E/D-mode logic circuits.展开更多
In the mammalian brain, information encoding and storage have been explained by revealing the cellular and molecular mechanisms of synaptic plasticity at various levels in the central nervous system, including the hip...In the mammalian brain, information encoding and storage have been explained by revealing the cellular and molecular mechanisms of synaptic plasticity at various levels in the central nervous system, including the hippocampus and the cerebral cortices. The modulatory mechanisms of synaptic excitability that are correlated with neuronal tasks are fundamental factors for synaptic plasticity, and they are dependent on intracellular Ca2＋-mediated signaling. In the present review, the A-type K＋ （IA） channel, one of the voltage-dependent cation channels, is considered as a key player in the modulation of Ca2＋ influx through synaptic NMDA receptors and their correlated signaling pathways. The cellular functions of IA channels indicate that they possibly play as integral parts of synaptic and somatic complexes, completing the initiation and stabilization of memory.展开更多
[Objectives] To study the effects of Tiaomaiyin and its disassembled prescription on expression of L-type calcium channel β2 subunit in rat model of tachyarrhythmia. [Methods] Sixty Wistar rats were randomly divided ...[Objectives] To study the effects of Tiaomaiyin and its disassembled prescription on expression of L-type calcium channel β2 subunit in rat model of tachyarrhythmia. [Methods] Sixty Wistar rats were randomly divided into model group,Tiaomaiyin prescription group( whole prescription group),main efficacy group of removing heat to cool blood( blood cooling group),and auxiliary drug efficacy group of benefiting qi and nourishing heart( qi benefiting group),auxiliary efficacy group of promoting flow of qi and blood circulation( qi flow promoting group),and amiodarone group( western medicine group). Aconitine was given 7 d after the intragastric administration of the corresponding drugs,and the time of occurrence of arrhythmia in each group was observed. The left ventricular myocardium was subjected to reverse transcription-polymerase chain reaction and Western blotting. [Results] The ventricular premature beats( VPB) time in the whole prescription group and western medicine group was significantly longer than that in the model group. Ventricular tachycardia( VT),ventricular fibrillation( VF),and cardiac arrest( CA) were longer in the whole prescription group,blood cooling group,and western medicine group. The mRNA and protein expression of L-type calcium channel β2 subunit in the whole prescription group,blood cooling group and western medicine group were significantly decreased. [Conclusions] Tiaomaiyin whole prescription group and blood cooling group can reduce the occurrence time of tachyarrhythmia and reduce the expression of LTCC β2 in myocardium.展开更多
Human neuroblastoma cells （SH-SY5Y） have similar structures and functions as neural cells and have been frequently used for cell culture studies of neural cell functions.Previous studies have revealed L-and N-type c...Human neuroblastoma cells （SH-SY5Y） have similar structures and functions as neural cells and have been frequently used for cell culture studies of neural cell functions.Previous studies have revealed L-and N-type calcium channels in SH-SY5Y cells.However,the distribution of the low-voltage activated calcium channel （namely called T-type calcium channel,including Cav3.1,Cav3.2,and Cav3.3） in SH-SY5Y cells remains poorly understood.The present study detected mRNA and protein expres-sion of the T-type calcium channel （Cav3.1,Cav3.2,and Cav3.3） in cultured SH-SY5Y cells using real-time polymerase chain reaction （PCR） and western blot analysis.Results revealed mRNA and protein expression from all three T-type calcium channel subtypes in SH-SY5Y cells.Moreover,Cav3.1 was the predominant T-type calcium channel subtype in SH-SY5Y cells.展开更多
Background L-type calcium channel participates in the regulation of a variety of physical and pathological process. In vasculature, it mainly mediated agonist-induced vascular smooth muscle contraction. However, it is...Background L-type calcium channel participates in the regulation of a variety of physical and pathological process. In vasculature, it mainly mediated agonist-induced vascular smooth muscle contraction. However, it is not clear whether there are differences in L-type calcium channel mediated vessel responses to certain vasoconstrictors among different species. Methods The coronary arteries were dissected from the heart of rats and mice respectively. The coronary arterial ring contraction was measured by Multi Myograph System. Results Endothelin-1, U46619 and 5-HT could produce concentration-dependent vasoconstriction of coronary arterial rings from rats and mice. Compared with rats, the vessel rings of mice were more sensitive to ET-1 and U46619, and less sensitive to 5-HT. The L-type Ca2~ channel blocker nifedipine could significantly inhibit the coronary artery contractions induced by ET-1, U46619 and 5-HT. The inhibitory effect of i ixM nifedipine on ET-1 and 5-HT-induced coronary artery contractions were stronger in mice than in rats, but its effect on U46619 induced-vessel contractions was much weaker in mice than in rats. Conclusions L-type Ca2＋ channel plays an important role in the coronary arterial contraction, but the responses to vasoconstrictor and L-type Ca2＋ channel blocker are different between rats and mice, thus suggesting that the coronary arteries of rats and mice have different biological characteristics.展开更多
Experimental data have shown that antiepileptic drugs cause neurodegeneration in developing rats. Valproate (VPA) is the drug of choice in primary generalized epilepsies, and carbamazepine (CBZ) is one of the most pre...Experimental data have shown that antiepileptic drugs cause neurodegeneration in developing rats. Valproate (VPA) is the drug of choice in primary generalized epilepsies, and carbamazepine (CBZ) is one of the most prescribed drugs in partial seizures. These drugs block sodium channels, thereby reducing sustained repetitive neuronal firing. The intracellular mechanisms whereby AEDs induce neuronal cell death are unclear. We examined whether AEDs induce apoptotic cell death in cultured cortical cells and whether calcium ions are involved in the AED-induced cell death. VPA and CBZ increased apoptotic cell death and induced morphological changes that were characterized by cell shrinkage and nuclear condensation or fragmentation. Incubation of cortical cultures with VPA or CBZ decreased phospho-Akt levels. CBZ decreased the intracellular calcium levels. On the other hand, FPL64176, an L-type calcium channel activator, increased the intracellular calcium levels and prevented the AED-induced apoptosis. Glycogen synthase kinase-3 inhibitors, such as alsterpaullone and azakenpaullone, prevented the AED-induced apoptosis. These results suggest that intracellular calcium level changes are associated with AEDs and apoptosis and that the activation of glycogen synthase kinase-3 is involved in the death of rat cortical neurons.展开更多
This paper presents an analysis of dispersion of dynamic biochemical signals in steady flow in a shallow Y-type microfluidic channel. A method is presented to control the flow widths of two steady flows in the Y-type ...This paper presents an analysis of dispersion of dynamic biochemical signals in steady flow in a shallow Y-type microfluidic channel. A method is presented to control the flow widths of two steady flows in the Y-type microchannel from two inlets.The transfer function for the Y-type microchannel is given by solving the governing equation for the Taylor-Aris dispersion in the microchannel. The amplitude-frequency and phase-frequency relations are provided which show that a shallow Y-type microchannel acts as a low-pass filter. The transports of different dynamic biochemical signals are investigated. In comparison with a fully mixing microfluidic channel, the magnitudes of the dynamic signals at the outlets in a Y-type microchannel are much smaller than those in a fully mixing microchannel, which demonstrates that the amplitude attenuation in a Y-type microchannel is larger than that of a fully mixing microchannel due to the transverse molecular diffusion. In order to control the desired signal in a microchannel, the solution of the inverse problem for the channel is also presented.展开更多
Neuropathic pain has been hypothesized to be the result of aberrant expression and function of sodium channels at the site of injury. To investigate the effects of NaV1.8 antisense oligonucleotide on the expression of...Neuropathic pain has been hypothesized to be the result of aberrant expression and function of sodium channels at the site of injury. To investigate the effects of NaV1.8 antisense oligonucleotide on the expression of sodium channel mRNA in dorsal root ganglion （DRG） neurons in chronic neuropathic pain. 24 Sprague-Dawley rats weighing 200--260 g were anesthetized with the intraperitoneal injection of 300 mg· kg^-1 choral hydrate. The CCI model was made by loose ligation of sciatic nerve trunk by 4--0 chromic gut. The mechanical and thermal pain threshold were measured before operation and 1, 3, 5, 7, 9, 11, 13 days after operation. A PE-10 catheter was implanted in subarachnoid space at lumbar region. On the 7th postoperative day the animals were randomly divided into 4 groups. The drugs were injected intrathecally twice a day for 5 consecutive days in group 2--4. The animals were decapitated 14 days after the surgery. The L4--L6 DRG of the operated side was removed and crushed, and total RNA was extracted with Trizol reagent. The contralateral side was used as control. The change of NaV1.8 sodium channel transcripts was determined by RT-PCR. Pain threshold was significantly lowered after CCI as compared with that in control group and was elevated 3 days after antisense oligonucleotide injection. Sensory neuron specific TTX-R sodium channel NaV1.8 transcript was down-regulated after antisense oligonucleotide injection at the dosage of 45 μg as compared with that in CCI group （P〈0.01）, and it was even greater at the dosage of 90 μg. The intrathecally injected NaV1.8 antisense oligonucleotide can reduce the mechanical allodynia and thermal hyperalgesia partially by downregulating the SNS transcript expression.展开更多
AIM:To investigate the effect of hydrogen sulfide(H2S)on smooth muscle motility in the gastric fundus.METHODS:The expression of cystathionineβ-synthase(CBS)and cystathionineγ-lyase(CSE)in cultured smooth muscle cell...AIM:To investigate the effect of hydrogen sulfide(H2S)on smooth muscle motility in the gastric fundus.METHODS:The expression of cystathionineβ-synthase(CBS)and cystathionineγ-lyase(CSE)in cultured smooth muscle cells from the gastric fundus was examined by the immunocytochemistry technique.The tension of the gastric fundus smooth muscle was recorded by an isometric force transducer under the condition of isometric contraction with each end of the smooth muscle strip tied with a silk thread.Intracellular recording was used to identify whether hydrogen sulfide affects the resting membrane potential of the gastric fundus in vitro.Cells were freshly separated from the gastric fundus of mice using a variety of enzyme digestion methods and whole-cell patch-clamp technique was used to find the effects of hydrogen sulfide on voltage-dependent potassium channel and calcium channel.Calcium imaging with fura-3AM loading was used to investigate the mechanism by which hydrogen sulfide regulates gastric fundus motility in cultured smooth muscle cells.RESULTS:We found that both CBS and CSE were expressed in the cul tured smooth muscle cel ls from the gastric fundus and that H2S increased the smooth muscle tension of the gastric fundus in mice at low concentrations.In addition,nicardipine and aminooxyacetic acid(AOAA),a CBS inhibitor,reduced the tension,whereas Nω-nitro-L-arginine methyl ester,a nonspecific nitric oxide synthase,increased the tension.The AOAA-induced relaxation was significantly recovered by H2S,and the Na HS-induced increase in tonic contraction was blocked by 5 mmol/L4-aminopyridine and 1μmol/L nicardipine.Na HS significantly depolarized the membrane potential and inhibited the voltage-dependent potassium currents.Moreover,Na HS increased L-type Ca2+currents and caused an elevation in intracellular calcium([Ca2+]i).CONCLUSION:These findings suggest that H2S may be an excitatory modulator in the gastric fundus in mice.The excitatory effect is mediated by voltagedependent potassium and L-type calcium channels.展开更多
Iron overload can lead to iron deposits in many tissues,particularly in the heart.It has also been shown to be associated with elevated oxidative stress in tissues.Elevated cardiac iron deposits can lead to iron overl...Iron overload can lead to iron deposits in many tissues,particularly in the heart.It has also been shown to be associated with elevated oxidative stress in tissues.Elevated cardiac iron deposits can lead to iron overload cardiomyopathy,a condition which provokes mortality due to heart failure in iron-overloaded patients.Currently,the mechanism of iron uptake into cardiomyocytes is still not clearly understood.Growing evidence suggests L-type Ca2+channels(LTCCs)as a possible pathway for ferrous iron(Fe2+)uptake into cardiomyocytes under iron overload conditions.Nevertheless,controversy still exists since some findings on pharmacological interventions and those using different cell types do not support LTCC’s role as a portal for iron uptake in cardiac cells.Recently,T-type Ca2+channels (TTCC)have been shown to play an important role in the diseased heart.Although TTCC and iron uptake in cardiomyocytes has not been investigated greatly,a recent finding indicated that TTCC could be an important portal in thalassemic hearts.In this review,comprehensive findings collected from previous studies as well as a discussion of the controversy regarding iron uptake mechanisms into cardiomyocytes via calcium channels are presented with the hope that understanding the cellular iron uptake mechanism in cardiomyocytes will lead to improved treatment and prevention strategies,particularly in iron-overloaded patients.展开更多
The pathogenesis of the second major neurodegenerative disorder, Parkinson’s disease(PD), is closely associated with the dysfunction of potassium(K~+ ) channels. Therefore, PD is also considered to be an ion channel ...The pathogenesis of the second major neurodegenerative disorder, Parkinson’s disease(PD), is closely associated with the dysfunction of potassium(K~+ ) channels. Therefore, PD is also considered to be an ion channel disease or neuronal channelopathy. Mounting evidence has shown that K~+ channels play crucial roles in the regulations of neurotransmitter release, neuronal excitability, and cell volume. Inhibition of K~+ channels enhances the spontaneous firing frequency of nigral dopamine(DA)neurons, induces a transition from tonic firing to burst discharge, and promotes the release of DA in the striatum.Recently, three K~+ channels have been identified to protect DA neurons and to improve the motor and non-motor symptoms in PD animal models: small conductance(SK)channels, A-type K~+ channels, and KV7/KCNQ channels.In this review, we summarize the physiological and pharmacological effects of the three K~+ channels. We also describe in detail the laboratory investigations regarding K~+ channels as a potential therapeutic target for PD.展开更多
The myocardial protection afforded by ischernic preconditioning （IPC） can alleviate ischemi- a-repel-fusion injury in normal rat heart. However, this myocardial protection is seldom studied in the type 2 diabetic ra...The myocardial protection afforded by ischernic preconditioning （IPC） can alleviate ischemi- a-repel-fusion injury in normal rat heart. However, this myocardial protection is seldom studied in the type 2 diabetic rat with myocardial ischemia disease. In this study, we aimed to evaluate the effects of ATP-sensitive potassium channels （KATP channels） on IPC in the isolated type 2 diabetic rat heart and the role of the sul- fonylurea gliclazide. Methods Streptozotocin（STZ）-induced type 2 diabetic male Wistar rats with or without gliclazide （64 mg/kg body weight, orally） and age-matched non-diabetic control rats were used for all studies. The isolated hearts were perfused with Langendorff＇s system under the constant flow, pressure and tempera- ture conditions with Kreb＇s-Henseleit solution （K-H）. After 5 minutes of balance peffusion, these rats were randomly divided into six groups： non-diabetic control rats without IPC （CIR） ; non-diabetic control rats with IPC （CIP）; diabetic rats without 1PC （DIR）; diabetic rats with IPC （DIP）; gliclazide-treated diabetic rats without IPC （GIR）; and gliclazide-treated diabetic rats with IPC （GIP）. Groups CIR, DIR, and GIR were subjected to 30-rain global ischemia and 60-rain reperfusion for induction of ischemia/reperfusion injury. Groups CIP, DIP, and GIP were given three cycles of 5-min ischemia and 5-rain reperfusion as IPC, and then ischemia/reperfusion injury program was implemented. Extent of ischemia/reperfusion injury was measured in terms of the release of lactate dehydrogenase （LDH）, creatine kinase （CK）, and creatin kinase-MB （CK- MB） in coronary effluent. After perfusion, Kir6.2 and SUR2A mRNA expressions in the myocardial tissue were characterized by fluorescent quantitative real-time PCR method, and Kir6.2 and SUR2A protein expres- sions were assessed by immunohistochemistry. Result In non-diabetic control rats, the release of LDH, CK, and CK-MB in coronary effluent markedly decreased with IPC compared with No-IPC （P 〈 0.05）, but not in diabetic rats. However, in gliclazide-treated diabetic rats, IPC-induced decrease in the release of LDH, CK, and CK-MB was restored compared with No-IPC （P 〈 0.05）. The expressions of Kir6.2 both at mRNA and protein levels in CIP were significantly higher than those in CIR. There was no significant difference in theexpression of Kir6.2 and SUR2A both at mRNA and protein levels between DIP and DIR. However, the expression of Kir6.2 both at mRNA and protein levels was significantly higher in GIP than in GIR. No significant difference was detected in the mRNA expression level of SUR2A between the six groups. The expression of SUR2A at protein level was significantly higher in CIP than in CIR and in GIP than in GIR. Conclusions The cardioprotective effect of IPC is abolished in the isolated type 2 diabetic rats compared with non-diabetic control rats. However, to some extent, gliclazide can improve the myocardial protection of IPC against ischemia/reperfusion injury, thus suggesting that it is mediated mainly by KATP channels at mRNA or protein level, which provides a basis for further investigating the effects of KATP channels on IPC.展开更多
基金supported by the Major Projects on Control and Rectification of Water Body Pollution of China (No. 2009ZX07317-006)the National Natural Science Foundation of China (No. 41001347, 40971259)+3 种基金the China Postdoctoral Science Foundation (No. 20100470759)the Shanghai Postdoctoral Scientific Program (No. 10R21412300)the Program of Shanghai Subject Chief Scientist (No. 10XD1401600)the International Cooperation Program of Ministry Science and Technology Development of Sino-Germany (No. 2007DFA90510)
文摘To explore eutrophication and algal bloom mechanisms in channel type reservoirs, a novel enclosure experiment was conducted by changing light intensity （LI） in the Daning River of the Three Gorges Reservoir （TGR）. Square enclosures （side 5.0 m） were covered on the surface with shading materials of different thickness, and with their bases open to the river. Changes and characteristics of the main eutrophication factors under the same water quality and hydrodynamic conditions but different LI were evaluated. All experimental water samples were neutral and alkalescent, with high nitrogen and phosphate concentrations, low potassium permanganate index, stable water quality, and different LI. At the same water depth, LI decreased with increasing shade material, while dissolved oxygen and water temperature were both stable. The growth peak of phytoplankton was with light of 345-4390 lux underwater or 558-7450 lux above the water surface, and water temperature of 25.6--26.5℃. Algae were observed in all water samples, accounting for 6 phylum and 57 species, with algal density changing frequently. The results showed that significantly strong or weak light was unfavorable for phytoplankton growth and the function together with suitable temperature and LI and ample sunshine encouraged algal blooms under the same water quality and hydrodynamic conditions. Correlation analysis indicated that algae reduced gradually lengthwise along water depth in the same enclosure while pH became high. The power exponent relationship between chlorophyll a （Chl-a） and LI was found by curve fitting, that is Chl-a = K（LI）n.
基金supported by the National Nature Science Foun-dation of China(Grant No.50879014)the Doctoral Program of Higher Education of China(Grant No.200802170010)
文摘This paper studies the hydrodynamic performance of a channel type planing trimaran. A numerical simulation is carried out based on a RANS-VOF solver to analyze the hydrodynamic performance of the channel type planing trimaran. A series of hydrodynamic experiments in towing tank were carried out, in which both the running attitude and the resistance performance of the trimaran model were recorded. Some hydrodynamic characteristics of the channel type planning trimaran are shown by the results. Firstly, the resistance declines significantly, with the forward speed across the high-speed resistance peak due to the combined effects of the aerodynamic and hydrodynamic lifts. Secondly, the resistance performance is influenced markedly by the longitudinal positio- ns of centre of the gravity and the displacements. Besides, the pressure distribution on the hull and the two-phase flow in the channel are discussed in the numerical simulations.
基金supported by grants from the National Natural Science Foundation of China (81171042,81070893 and 81221002)the Beijing Outstanding Ph.D.Program Mentor Grantthe Specialized Research Fund for Doctoral Programs of Higher Education, China(20110001110058)
文摘Objective Formaldehyde at high concentrations is a contributor to air pollution. It is also an endogenous metabolic product in cells, and when beyond physiological concentrations, has pathological effects on neurons. Formaldehyde induces mis-folding and aggregation of neuronal tau protein, hippocampal neuronal apoptosis, cognitive impairment and loss of memory functions, as well as excitation of peripheral nociceptive neurons in cancer pain models. Intracellular calcium （[Ca2＋]i） is an important intracellular messenger, and plays a key role in many pathological processes. The present study aimed to investigate the effect of formaldehyde on [Ca2＋]i and the possible involvement of N-methyl-D-aspartate receptors （NMDARs） and T-type Ca2＋ channels on the cell membrane. Methods Using primary cultured hippocampal neurons as a model, changes of [Ca2＋]i in the presence of formaldehyde at a low concentration were detected by confocal laser scanning microscopy. Results Formaldehyde at 1 mmol/L approximately doubled [Ca2＋]i. （2R）-amino-5-phosphonopentanoate （AP5, 25 μmol/L, an NMDAR antagonist） and mibefradil （MIB, 1 μmol/L, a T-type Ca2＋ channel blocker）, given 5 min after formaldehyde perfusion, each partly inhibited the formaldehyde-induced increase of [Ca：＋]i, and this inhibitory effect was reinforced by combined application of AP5 and MIB. When applied 3 min before formaldehyde perfusion, AP5 （even at 50μmol/L） did not inhibit the formaldehyde-induced increase of [Ca2＋]i, but MIB （1 μmol/L） significantly inhibited this increase by 70%. Conclusion These results suggest that formaldehyde at a low concentration increases [Ca2＋]i in cultured hippocampal neurons; NMDARs and T-type Ca2＋ channels may be involved in this process.
文摘Intracellular cAMP and Ca^2＋ are involved in the regulation of steroidogenic activity in Leydig cells, which coordinate responses to luteinizing hormone （LH） and human ehorionic gonadotropin （hCG）. However, the identification of Ca^2＋ entry implicated in Leydig cell steroidogenesis is not well defined. The objective of this study was to identify the type of Ca^2＋ channel that affects Leydig cell steroidogenesis. In vitro steroidogenesis in the freshly dissociated Leydig cells of mice was induced by hCG incubation. The effects of mibefradil （a putative T-type Ca^2＋ channel blocker） on steroidogenesis were assessed using reverse transcription （RT）-polymerase chain reaction analysis for the steroidogenic acute regulatory protein （STAR） mRNA expression and testosterone production using radioimmunoassay. In the presence of 1.0 mmol L-1 extracellular Ca^2＋, hCG at 1 to 100 IU noticeably elevated both StAR mRNA level and testosterone secretion （P 〈 0.05）, and the stimulatory effects of hCG were markedly diminished by mibefradil in a dose-dependent manner （P 〈 0.05）. Moreover; the hCG-induced increase in testosterone production was completely removed when external Ca^2＋ was omitted, implying that Ca entry is needed for hCG-induced steroidogenesis. Furthermore, a patch-clamp study revealed the presence of mibefradil-sensitive Ca^24- currents seen at a concentration range that nearly paralleled those inhibiting steroidogenesis. Collectively, Our data provide evidence that hCG-stimulated steroidogenesis is mediated at least in part by Ca^2＋ entry carried out by the T-type Ca^2＋ channel in the Leydig cells of mice.
基金supported by National Natural Science Foundation of China(No.81470440)Guangdong Natural Science Foundation(No.S2013010016256)Medical Scientific Research Foundation of Guangdong Province(No.A2013049)
文摘Background Atrial fibrillation （AF） is the most common sustained cardiac arrhythmia without effective treatment. AF is associated with atrial conduction disturbances caused by electrical and / or structural remodeling. But the role of connexin （Cx） 43 in the regulation of L type calcium channel （LCC） remains unclear. We hypothesized that Cx 43 might co-localize and regulate the L type calcium channel current （ICa, D. Methods Real-time PCR and whole-cell patch clamp were used to detect the expression of LCC lc subunit and the cur rent density of Ica, L, before and after Cx 43 knocking down respectively. The co-localization of Cx 43 with LCC was investigated by co-immunoprecipitation and confocal microscopy. Results Knocking down of Cx43 significantly inhibited the current density of ICa, L through decreasing the gene expression of LCC alc in cul tured atrium-derived myocytes （HL-1 cells）. Cx43 co-localized with LCC eric subunit in atrial myocytes. Conclusions Cx 43 regulates the ICa, L in atrial myoctyes through LCC, representing a potential pathogenic mechanism in atrial arrhythmias.
基金supported by the National Science and Technology Major Project,China(Grant No.2013ZX02308-002)the National Natural Science Foundation of China(Grant Nos.11435010,61474086,and 61404099)
文摘A novel groove-type channel enhancement-mode AlGaN/GaN MIS high electron mobility transistor（GTCE-HEMT）with a combined polar and nonpolar AlGaN/GaN heterostucture is presented. The device simulation shows a threshold voltage of 1.24 V, peak transconductance of 182 m S/mm, and subthreshold slope of 85 m V/dec, which are obtained by adjusting the device parameters. Interestingly, it is possible to control the threshold voltage accurately without precisely controlling the etching depth in fabrication by adopting this structure. Besides, the breakdown voltage（VB） is significantly increased by 78% in comparison with the value of the conventional MIS-HEMT. Moreover, the fabrication process of the novel device is entirely compatible with that of the conventional depletion-mode（D-mode） polar AlGaN/GaN HEMT. It presents a promising way to realize the switch application and the E/D-mode logic circuits.
基金supported by the 2014 Scientific Promotion Program funded by Jeju National University, Korea
文摘In the mammalian brain, information encoding and storage have been explained by revealing the cellular and molecular mechanisms of synaptic plasticity at various levels in the central nervous system, including the hippocampus and the cerebral cortices. The modulatory mechanisms of synaptic excitability that are correlated with neuronal tasks are fundamental factors for synaptic plasticity, and they are dependent on intracellular Ca2＋-mediated signaling. In the present review, the A-type K＋ （IA） channel, one of the voltage-dependent cation channels, is considered as a key player in the modulation of Ca2＋ influx through synaptic NMDA receptors and their correlated signaling pathways. The cellular functions of IA channels indicate that they possibly play as integral parts of synaptic and somatic complexes, completing the initiation and stabilization of memory.
基金Supported by the Project of Beijing Municipal Natural Science Foundation(7173261)
文摘[Objectives] To study the effects of Tiaomaiyin and its disassembled prescription on expression of L-type calcium channel β2 subunit in rat model of tachyarrhythmia. [Methods] Sixty Wistar rats were randomly divided into model group,Tiaomaiyin prescription group( whole prescription group),main efficacy group of removing heat to cool blood( blood cooling group),and auxiliary drug efficacy group of benefiting qi and nourishing heart( qi benefiting group),auxiliary efficacy group of promoting flow of qi and blood circulation( qi flow promoting group),and amiodarone group( western medicine group). Aconitine was given 7 d after the intragastric administration of the corresponding drugs,and the time of occurrence of arrhythmia in each group was observed. The left ventricular myocardium was subjected to reverse transcription-polymerase chain reaction and Western blotting. [Results] The ventricular premature beats( VPB) time in the whole prescription group and western medicine group was significantly longer than that in the model group. Ventricular tachycardia( VT),ventricular fibrillation( VF),and cardiac arrest( CA) were longer in the whole prescription group,blood cooling group,and western medicine group. The mRNA and protein expression of L-type calcium channel β2 subunit in the whole prescription group,blood cooling group and western medicine group were significantly decreased. [Conclusions] Tiaomaiyin whole prescription group and blood cooling group can reduce the occurrence time of tachyarrhythmia and reduce the expression of LTCC β2 in myocardium.
基金the National Natural Science Foundation of China,No.81100831the Medical Science Foundation of Guangdong Health Department,No.B2011303
文摘Human neuroblastoma cells （SH-SY5Y） have similar structures and functions as neural cells and have been frequently used for cell culture studies of neural cell functions.Previous studies have revealed L-and N-type calcium channels in SH-SY5Y cells.However,the distribution of the low-voltage activated calcium channel （namely called T-type calcium channel,including Cav3.1,Cav3.2,and Cav3.3） in SH-SY5Y cells remains poorly understood.The present study detected mRNA and protein expres-sion of the T-type calcium channel （Cav3.1,Cav3.2,and Cav3.3） in cultured SH-SY5Y cells using real-time polymerase chain reaction （PCR） and western blot analysis.Results revealed mRNA and protein expression from all three T-type calcium channel subtypes in SH-SY5Y cells.Moreover,Cav3.1 was the predominant T-type calcium channel subtype in SH-SY5Y cells.
基金supported by the National Natural Science Foundation of China(No81273516,No 81070102,No 81302779)by Guangdong Provincial TCM Science Foundation(20122180)by Guangdong Provincial Medical Science Foundation(NoA2012006)
文摘Background L-type calcium channel participates in the regulation of a variety of physical and pathological process. In vasculature, it mainly mediated agonist-induced vascular smooth muscle contraction. However, it is not clear whether there are differences in L-type calcium channel mediated vessel responses to certain vasoconstrictors among different species. Methods The coronary arteries were dissected from the heart of rats and mice respectively. The coronary arterial ring contraction was measured by Multi Myograph System. Results Endothelin-1, U46619 and 5-HT could produce concentration-dependent vasoconstriction of coronary arterial rings from rats and mice. Compared with rats, the vessel rings of mice were more sensitive to ET-1 and U46619, and less sensitive to 5-HT. The L-type Ca2~ channel blocker nifedipine could significantly inhibit the coronary artery contractions induced by ET-1, U46619 and 5-HT. The inhibitory effect of i ixM nifedipine on ET-1 and 5-HT-induced coronary artery contractions were stronger in mice than in rats, but its effect on U46619 induced-vessel contractions was much weaker in mice than in rats. Conclusions L-type Ca2＋ channel plays an important role in the coronary arterial contraction, but the responses to vasoconstrictor and L-type Ca2＋ channel blocker are different between rats and mice, thus suggesting that the coronary arteries of rats and mice have different biological characteristics.
文摘Experimental data have shown that antiepileptic drugs cause neurodegeneration in developing rats. Valproate (VPA) is the drug of choice in primary generalized epilepsies, and carbamazepine (CBZ) is one of the most prescribed drugs in partial seizures. These drugs block sodium channels, thereby reducing sustained repetitive neuronal firing. The intracellular mechanisms whereby AEDs induce neuronal cell death are unclear. We examined whether AEDs induce apoptotic cell death in cultured cortical cells and whether calcium ions are involved in the AED-induced cell death. VPA and CBZ increased apoptotic cell death and induced morphological changes that were characterized by cell shrinkage and nuclear condensation or fragmentation. Incubation of cortical cultures with VPA or CBZ decreased phospho-Akt levels. CBZ decreased the intracellular calcium levels. On the other hand, FPL64176, an L-type calcium channel activator, increased the intracellular calcium levels and prevented the AED-induced apoptosis. Glycogen synthase kinase-3 inhibitors, such as alsterpaullone and azakenpaullone, prevented the AED-induced apoptosis. These results suggest that intracellular calcium level changes are associated with AEDs and apoptosis and that the activation of glycogen synthase kinase-3 is involved in the death of rat cortical neurons.
基金National Natural Science Foundation of Chinagrant number:11172060the Fundamental Research Funds for the Central Universities in China
文摘This paper presents an analysis of dispersion of dynamic biochemical signals in steady flow in a shallow Y-type microfluidic channel. A method is presented to control the flow widths of two steady flows in the Y-type microchannel from two inlets.The transfer function for the Y-type microchannel is given by solving the governing equation for the Taylor-Aris dispersion in the microchannel. The amplitude-frequency and phase-frequency relations are provided which show that a shallow Y-type microchannel acts as a low-pass filter. The transports of different dynamic biochemical signals are investigated. In comparison with a fully mixing microfluidic channel, the magnitudes of the dynamic signals at the outlets in a Y-type microchannel are much smaller than those in a fully mixing microchannel, which demonstrates that the amplitude attenuation in a Y-type microchannel is larger than that of a fully mixing microchannel due to the transverse molecular diffusion. In order to control the desired signal in a microchannel, the solution of the inverse problem for the channel is also presented.
文摘Neuropathic pain has been hypothesized to be the result of aberrant expression and function of sodium channels at the site of injury. To investigate the effects of NaV1.8 antisense oligonucleotide on the expression of sodium channel mRNA in dorsal root ganglion （DRG） neurons in chronic neuropathic pain. 24 Sprague-Dawley rats weighing 200--260 g were anesthetized with the intraperitoneal injection of 300 mg· kg^-1 choral hydrate. The CCI model was made by loose ligation of sciatic nerve trunk by 4--0 chromic gut. The mechanical and thermal pain threshold were measured before operation and 1, 3, 5, 7, 9, 11, 13 days after operation. A PE-10 catheter was implanted in subarachnoid space at lumbar region. On the 7th postoperative day the animals were randomly divided into 4 groups. The drugs were injected intrathecally twice a day for 5 consecutive days in group 2--4. The animals were decapitated 14 days after the surgery. The L4--L6 DRG of the operated side was removed and crushed, and total RNA was extracted with Trizol reagent. The contralateral side was used as control. The change of NaV1.8 sodium channel transcripts was determined by RT-PCR. Pain threshold was significantly lowered after CCI as compared with that in control group and was elevated 3 days after antisense oligonucleotide injection. Sensory neuron specific TTX-R sodium channel NaV1.8 transcript was down-regulated after antisense oligonucleotide injection at the dosage of 45 μg as compared with that in CCI group （P〈0.01）, and it was even greater at the dosage of 90 μg. The intrathecally injected NaV1.8 antisense oligonucleotide can reduce the mechanical allodynia and thermal hyperalgesia partially by downregulating the SNS transcript expression.
基金Supported by National Natural Science Foundation of China,No.31171107,No.31071011 and No.31271236
文摘AIM:To investigate the effect of hydrogen sulfide(H2S)on smooth muscle motility in the gastric fundus.METHODS:The expression of cystathionineβ-synthase(CBS)and cystathionineγ-lyase(CSE)in cultured smooth muscle cells from the gastric fundus was examined by the immunocytochemistry technique.The tension of the gastric fundus smooth muscle was recorded by an isometric force transducer under the condition of isometric contraction with each end of the smooth muscle strip tied with a silk thread.Intracellular recording was used to identify whether hydrogen sulfide affects the resting membrane potential of the gastric fundus in vitro.Cells were freshly separated from the gastric fundus of mice using a variety of enzyme digestion methods and whole-cell patch-clamp technique was used to find the effects of hydrogen sulfide on voltage-dependent potassium channel and calcium channel.Calcium imaging with fura-3AM loading was used to investigate the mechanism by which hydrogen sulfide regulates gastric fundus motility in cultured smooth muscle cells.RESULTS:We found that both CBS and CSE were expressed in the cul tured smooth muscle cel ls from the gastric fundus and that H2S increased the smooth muscle tension of the gastric fundus in mice at low concentrations.In addition,nicardipine and aminooxyacetic acid(AOAA),a CBS inhibitor,reduced the tension,whereas Nω-nitro-L-arginine methyl ester,a nonspecific nitric oxide synthase,increased the tension.The AOAA-induced relaxation was significantly recovered by H2S,and the Na HS-induced increase in tonic contraction was blocked by 5 mmol/L4-aminopyridine and 1μmol/L nicardipine.Na HS significantly depolarized the membrane potential and inhibited the voltage-dependent potassium currents.Moreover,Na HS increased L-type Ca2+currents and caused an elevation in intracellular calcium([Ca2+]i).CONCLUSION:These findings suggest that H2S may be an excitatory modulator in the gastric fundus in mice.The excitatory effect is mediated by voltagedependent potassium and L-type calcium channels.
基金Supported by Thailand Research Fund grants RTA5280006 (Chattipakorn N)BRG5480003(Chattipakorn S)+1 种基金the National Research Council of Thailand(Chattipakorn N)the Thai-land Research Fund Royal Golden Jubilee project(Kumfu S and Chattipakorn N)
文摘Iron overload can lead to iron deposits in many tissues,particularly in the heart.It has also been shown to be associated with elevated oxidative stress in tissues.Elevated cardiac iron deposits can lead to iron overload cardiomyopathy,a condition which provokes mortality due to heart failure in iron-overloaded patients.Currently,the mechanism of iron uptake into cardiomyocytes is still not clearly understood.Growing evidence suggests L-type Ca2+channels(LTCCs)as a possible pathway for ferrous iron(Fe2+)uptake into cardiomyocytes under iron overload conditions.Nevertheless,controversy still exists since some findings on pharmacological interventions and those using different cell types do not support LTCC’s role as a portal for iron uptake in cardiac cells.Recently,T-type Ca2+channels (TTCC)have been shown to play an important role in the diseased heart.Although TTCC and iron uptake in cardiomyocytes has not been investigated greatly,a recent finding indicated that TTCC could be an important portal in thalassemic hearts.In this review,comprehensive findings collected from previous studies as well as a discussion of the controversy regarding iron uptake mechanisms into cardiomyocytes via calcium channels are presented with the hope that understanding the cellular iron uptake mechanism in cardiomyocytes will lead to improved treatment and prevention strategies,particularly in iron-overloaded patients.
基金supported by the National Natural Science Foundation of China(31671054 and 81430024)the Postdoctoral Science Foundation of China(2017M610412)the Bureau of Science and Technology of Qingdao Municipality,China(17-1-1-44-jch)
文摘The pathogenesis of the second major neurodegenerative disorder, Parkinson’s disease(PD), is closely associated with the dysfunction of potassium(K~+ ) channels. Therefore, PD is also considered to be an ion channel disease or neuronal channelopathy. Mounting evidence has shown that K~+ channels play crucial roles in the regulations of neurotransmitter release, neuronal excitability, and cell volume. Inhibition of K~+ channels enhances the spontaneous firing frequency of nigral dopamine(DA)neurons, induces a transition from tonic firing to burst discharge, and promotes the release of DA in the striatum.Recently, three K~+ channels have been identified to protect DA neurons and to improve the motor and non-motor symptoms in PD animal models: small conductance(SK)channels, A-type K~+ channels, and KV7/KCNQ channels.In this review, we summarize the physiological and pharmacological effects of the three K~+ channels. We also describe in detail the laboratory investigations regarding K~+ channels as a potential therapeutic target for PD.
基金supported by the Qingdao Municipal Science and Technology Commission (No. 11-2-3-2-(12)-nsh)
文摘The myocardial protection afforded by ischernic preconditioning （IPC） can alleviate ischemi- a-repel-fusion injury in normal rat heart. However, this myocardial protection is seldom studied in the type 2 diabetic rat with myocardial ischemia disease. In this study, we aimed to evaluate the effects of ATP-sensitive potassium channels （KATP channels） on IPC in the isolated type 2 diabetic rat heart and the role of the sul- fonylurea gliclazide. Methods Streptozotocin（STZ）-induced type 2 diabetic male Wistar rats with or without gliclazide （64 mg/kg body weight, orally） and age-matched non-diabetic control rats were used for all studies. The isolated hearts were perfused with Langendorff＇s system under the constant flow, pressure and tempera- ture conditions with Kreb＇s-Henseleit solution （K-H）. After 5 minutes of balance peffusion, these rats were randomly divided into six groups： non-diabetic control rats without IPC （CIR） ; non-diabetic control rats with IPC （CIP）; diabetic rats without 1PC （DIR）; diabetic rats with IPC （DIP）; gliclazide-treated diabetic rats without IPC （GIR）; and gliclazide-treated diabetic rats with IPC （GIP）. Groups CIR, DIR, and GIR were subjected to 30-rain global ischemia and 60-rain reperfusion for induction of ischemia/reperfusion injury. Groups CIP, DIP, and GIP were given three cycles of 5-min ischemia and 5-rain reperfusion as IPC, and then ischemia/reperfusion injury program was implemented. Extent of ischemia/reperfusion injury was measured in terms of the release of lactate dehydrogenase （LDH）, creatine kinase （CK）, and creatin kinase-MB （CK- MB） in coronary effluent. After perfusion, Kir6.2 and SUR2A mRNA expressions in the myocardial tissue were characterized by fluorescent quantitative real-time PCR method, and Kir6.2 and SUR2A protein expres- sions were assessed by immunohistochemistry. Result In non-diabetic control rats, the release of LDH, CK, and CK-MB in coronary effluent markedly decreased with IPC compared with No-IPC （P 〈 0.05）, but not in diabetic rats. However, in gliclazide-treated diabetic rats, IPC-induced decrease in the release of LDH, CK, and CK-MB was restored compared with No-IPC （P 〈 0.05）. The expressions of Kir6.2 both at mRNA and protein levels in CIP were significantly higher than those in CIR. There was no significant difference in theexpression of Kir6.2 and SUR2A both at mRNA and protein levels between DIP and DIR. However, the expression of Kir6.2 both at mRNA and protein levels was significantly higher in GIP than in GIR. No significant difference was detected in the mRNA expression level of SUR2A between the six groups. The expression of SUR2A at protein level was significantly higher in CIP than in CIR and in GIP than in GIR. Conclusions The cardioprotective effect of IPC is abolished in the isolated type 2 diabetic rats compared with non-diabetic control rats. However, to some extent, gliclazide can improve the myocardial protection of IPC against ischemia/reperfusion injury, thus suggesting that it is mediated mainly by KATP channels at mRNA or protein level, which provides a basis for further investigating the effects of KATP channels on IPC.
