As a noninvasive technique,ultrasound stimulation is known to modulate neuronal activity both in vitro and in vivo.The latest explanation of this phenomenon is that the acoustic wave can activate the ion channels and ...As a noninvasive technique,ultrasound stimulation is known to modulate neuronal activity both in vitro and in vivo.The latest explanation of this phenomenon is that the acoustic wave can activate the ion channels and further impact the electrophysiological properties of targeted neurons.However,the underlying mechanism of low-intensity pulsed ultrasound(LIPUS)-induced neuro-modulation effects is still unclear.Here,we characterize the excitatory effects of LIPUS on spontaneous activity and the intracellular Ca^(2+)homeostasis in cultured hippocampal neurons.By whole-cell patch clamp recording,we found that 15 min of 1-MHz LIPUS boosts the frequency of both spontaneous action potentials and spontaneous excitatory synaptic currents(sEPSCs)and also increases the amplitude of sEPSCs in hippocampal neurons.This phenomenon lasts for>10 min after LIPUS exposure.Together with Ca^(2+)imaging,we clarified that LIPUS increases the[Ca^(2+)]cyto level by facilitating L-type Ca^(2+)channels(LTCCs).In addition,due to the[Ca^(2+)]cyto elevation by LIPUS exposure,the Ca^(2+)-dependent CaMKII-CREB pathway can be activated within 30 min to further regulate the gene transcription and protein expression.Our work suggests that LIPUS regulates neuronal activity in a Ca^(2+)-dependent manner via LTCCs.This may also explain the multi-activation effects of LIPUS beyond neurons.LIPUS stimulation potentiates spontaneous neuronal activity by increasing Ca^(2+)influx.展开更多
The characteristic impedances of L-type and T-type networks are first investigated for a distributed amplifier design.The analysis shows that the L-type network has better frequency characteristics than the T-type one...The characteristic impedances of L-type and T-type networks are first investigated for a distributed amplifier design.The analysis shows that the L-type network has better frequency characteristics than the T-type one.A distribution amplifier based on the L-type network is implemented with the 2-μm GaAs HBT（heterojunction-bipolar transistor） process of WIN semiconductors.The measurement result presents excellent bandwidth performance and gives a gain of 5.5 dB with a gain flatness of ±1dB over a frequency range from 3 to 18 GHz.The return losses S11 and S22 are below-10dB in the designed frequency range.The output 1-dB compression point at 5 GHz is 13.3 dBm.The chip area is 0.95 mm2 and the power dissipation is 95 mW under a 3.5 V supply.展开更多
In the present study, we aimed to evaluate the effects of cilnidipine and L-type calcium channel blockers（L-type CCBs） on renal function in hypertensive patients. The randomized controlled trials（RCTs） of cilnidip...In the present study, we aimed to evaluate the effects of cilnidipine and L-type calcium channel blockers（L-type CCBs） on renal function in hypertensive patients. The randomized controlled trials（RCTs） of cilnidipine and L-type CCBs on hypertension treatment were selected from Pubmed, Embase, Google Scholar, CNKI, Science Direct, Ebsco, Springer, Ovid, Cochrane Library, Medline, VIP and Wanfang databases（from the date of databases＇ establishment to September 2014）. Data were independently evaluated following the Jadad standard. The percentage changes of serum creatinine（SCr） value, urinary protein excretion（UPE）, urinary protein/creatinine ratio（UPCR） and estimated glomerular filtration rate（e GFR） pre- and post-treatment were extracted for the subsequent meta-analysis. The mean difference（MD） and the 95% confidence interval（95% CI） were determined using RevM an 5.3 software. A total of 10 RCTs of high quality were included and analyzed by fixedor random-effect models. The results indicated that UPE（MD = –36.59, 95% CI： –70.85, –2.33） or UPCR（MD = –46.56, 95% CI： –88.50, –4.62） was significantly reduced by cilnidipine compared with L-type CCBs. However, such significant difference was not detected in reduction of SCr（MD = 0.01, 95% CI： –2.97, 2.98） or eG FR（MD = 1.56, 95% CI： –0.19, 3.31）. Compared with L-type CCBs, cilnidipine was more effective in reducing proteinuria or preventing the proteinuria progression. In addition, we did not find significant differences in SCr and eG FR between the two groups.展开更多
In the present study,we investigated the mechanisms underlying the mediation of iron transport by Ltype Ca^2+ channels(LTCCs)in primary cultured ventral mesencephalon(VM)neurons from rats.We found that cotreatment wit...In the present study,we investigated the mechanisms underlying the mediation of iron transport by Ltype Ca^2+ channels(LTCCs)in primary cultured ventral mesencephalon(VM)neurons from rats.We found that cotreatment with 100 lmol/L FeSO4 and MPP^+(1-methyl-4-phenylpyridinium)significantly increased the production of intracellular reactive oxygen species,decreased the mitochondrial transmembrane potential and increased the caspase-3 activation compared to MPP^+ treatment alone.Co-treatment with 500 lmol/L CaCl2 further aggravated the FeSO4-induced neurotoxicity in MPP^+-treated VM neurons.Co-treatment with 10 lmol/L isradipine,an LTCC blocker,alleviated the neurotoxicity induced by co-application of FeSO4 and FeSO4/CaCl2.Further studies indicated that MPP^+treatment accelerated the iron influx into VM neurons.In addition,FeSO4 treatment significantly increased the intracellular Ca^2+ concentration.These effects were blocked by isradipine.These results suggest that elevated extracellular Ca^2+ aggravates ironinduced neurotoxicity.LTCCs mediate iron transport in dopaminergic neurons and this,in turn,results in elevated intracellular Ca^2+ and further aggravates iron-induced neurotoxicity.展开更多
Experimental tests were conducted to evaluate the hydrodynamic performance of an L-type podded propulsor in straight-ahead motion and off-design conditions using an open-water measuring instrument developed by the aut...Experimental tests were conducted to evaluate the hydrodynamic performance of an L-type podded propulsor in straight-ahead motion and off-design conditions using an open-water measuring instrument developed by the authors for podded propulsors, a ship model towing tank, and under water particle image velocimetry （PIV） measurement systems. Under the three types of conditions, the main parameters of an L-type podded propulsor were measured, including the propeller thrust and torque, as well as the thrust, side force, and moment of the whole pod unit.In addition, the flow field on the section between the propeller and the strut was analyzed. Experimental results demonstrate that the dynamic azimuthing rate and direction and the turning direction affect the forces on the propeller and the whole pod unit. Forces are asymmetrically distributed between the left and right azimuthing directions because of the effect of propeller rotation. The findings of this study provide a foundation for further research on L-type podded propulsors.展开更多
Objective To investigate the effect of ferulic acid,a natural compound,on pancreatic beta cell viability,Ca^(2+)channels,and insulin secretion.Methods We studied the effects of ferulic acid on rat insulinoma cell line...Objective To investigate the effect of ferulic acid,a natural compound,on pancreatic beta cell viability,Ca^(2+)channels,and insulin secretion.Methods We studied the effects of ferulic acid on rat insulinoma cell line viability using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide viability assay.The whole-cell patch-clamp technique and enzyme-linked immunosorbent assay were also used to examine the action of ferulic acid on Ca^(2+)channels and insulin secretion,respectively.Results Ferulic acid did not affect cell viability during exposures up to 72 h.The electrophysiological study demonstrated that ferulic acid rapidly and concentration-dependently increased L-type Ca^(2+)channel current,shifting its activation curve in the hyperpolarizing direction with a decreased slope factor,while the voltage dependence of inactivation was not affected.On the other hand,ferulic acid have no effect on T-type Ca^(2+)channels.Furthermore,ferulic acid significantly increased insulin secretion,an effect inhibited by nifedipine and Ca^(2+)-free extracellular fluid,confirming that ferulic acid-induced insulin secretion in these cells was mediated by augmenting Ca^(2+)influx through L-type Ca^(2+)channel.Our data also suggest that this may be a direct,nongenomic action.Conclusion This is the first electrophysiological demonstration that acute ferulic acid treatment could increase L-type Ca^(2+)channel current in pancreaticβcells by enhancing its voltage dependence of activation,leading to insulin secretion.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
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
Sigma-1 receptors are unique receptors that are postulated to act as intracellular amplifiers for signal transduction within cells of the nervous system. The present paper studied the
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
Objectives Heart failure （HF） is one of the most common outcome for all kinds of heart diseases, the effects of energetic therapy on HF remains controversial, especially to ischemic HF. The aim of this study was to ...Objectives Heart failure （HF） is one of the most common outcome for all kinds of heart diseases, the effects of energetic therapy on HF remains controversial, especially to ischemic HF. The aim of this study was to explore the effect of exogenous phosphocreatine with different concentration on L-type calcium（I Cc-L） current in ischemic ventricular myocytes of guinea pig and to investigate its underlying electrophysiological mechanism for the treatment of ischemic HF. Methods Single ventricular myocytes were isolated enzymatically from left ventricle of guinea pig. Peak I Ca-L current were recorded using patch clamp techniques in the whole-cell configuration when myocytes had been superfused with normal Tyrode solution, simple ischemic solution, ischemic solution containing phosphocreatine with different concentration for 10 minutes respectively. Results Peak I Ca-L current density of myocytes superfused with simple simulated ischemic solution was remarkably inhibited by 80.6 ± 5.2% compared with myocytes superfused with normal Tyrode solution（P〈0.05）. Ischemic solution containing phosphocreatine of 5, 10, 20, 30mmol/L inhibited Peak I Ca-L current density by （53.8±6.7）%, （41.8 ± 8.2）%, （38.1±7.4）%, （36.6±9.7）% respectively. There was no statistical significance among phosphocreation of 10, 20, 30 mmol / L. Conclusions Extrogenous phosphocreatine could reverse the inhibition of I Ca-L current under ischemic condition, which could be the ionic basis for the treatment of ischemic heart failure. 0-10 mmol/L phosphocreatine exerted significant dose-effect relationship which no longer existed as concentration more than 10 mmol/L. It is supposed that phosphocreatine increased I Ca-L current by many pathways rather than simple substrate for ATP synthesis.展开更多
Objective:To study hesperetin-induced vasorelaxation after depolarizing contraction in human umbilical veins(HUVs)to elucidate the role of L-type Ca^(2+)channel(LTCC)and related signaling pathway.Methods:Isometric ten...Objective:To study hesperetin-induced vasorelaxation after depolarizing contraction in human umbilical veins(HUVs)to elucidate the role of L-type Ca^(2+)channel(LTCC)and related signaling pathway.Methods:Isometric tension recording was performed in HUV rings pre-contracted with K^(+).Hesperetin relaxing mechanism was investigated using a LTCC opener(BayK8644)and blockers of cyclic nucleotides and phosphodiesterases(PDEs).Whole-cell patch-clamping in A7r5 cells,a rat vascular smooth muscle cell line,was performed to study the effect of hesperetin on LTCC current.Results:After depolarizing precontraction,hesperetin induced HUV relaxation concentration-dependently and endothelium-independently;1 mmol/L hesperetin reduced denuded HUV ring tension by 68.7%±4.3%compared to matching vehicle,osmolality,and time controls(P<0.0001).Importantly,hesperetin competitively inhibited BayK8644-induced contraction,shifting the half maximal effective concentration of BayK8644 response from 1.08 nmol/L[95%confidence interval(CI)0.49-2.40]in vehicle control to11.30 nmol/L(95%CI 5.45-23.41)in hesperetin(P=0.0001).Moreover,hesperetin elicited further vasorelaxation in denuded HUV rings pretreated with inhibitors of soluble guanylyl cyclase,adenylyl cyclase,PDE3,PDE4,and PDE5(P<0.01),while rings pretreated with PDE1 inhibitors could not be relaxed by hesperetin(P>0.05).However,simultaneously applying inhibitors of soluble guanylyl cyclase and adenylyl cyclase could not inhibit hesperetin's effect(P>0.05).In whole-cell patch-clamping,hesperetin rapidly decreased LTCC current in A7r5 cells to66.7%±5.8%(P=0.0104).Conclusions:Hesperetin diminishes depolarizing contraction of human vascular smooth muscle through inhibition of LTCC,and not cyclic nucleotides nor PDEs.Our evidence supports direct LTCC interaction and provides additional basis for the use of hesperetin and its precursor hesperidin as vasodilators and may lead to future vasodilator drug development as a treatment alternative for cardiovascular diseases.展开更多
Background It has been proved that sevoflurane postconditioning （SpostC） could protect the heart against myocardial ischemia/reperfusion injury, however, there has been few research focused on the electrophysiologic...Background It has been proved that sevoflurane postconditioning （SpostC） could protect the heart against myocardial ischemia/reperfusion injury, however, there has been few research focused on the electrophysiological effects of SpostC. The objective of the study was to investigate the effects of SpostC on action potential duration （APD） and L-type calcium current （Ica, L） in isolated cardiomyocytes. Methods Langendorff perfused SD rat hearts were randomly assigned to one of the time control （TC）, ischemia/reperfusion （I/R, 25 minutes of ischemia followed by 30 minutes of reperfusion）, and SpostC （postconditioned with 3% sevoflurane） groups. At the end of reperfusion, epicardial myocytes were dissociated enzymatically for patch clamp studies. Results Sevoflurane directly prolonged APD and decreased peak Ica, L densities in epicardial myocytes of the TC group （P〈0.05）. I/R injury shortened APD and decreased peak Ica, L densities in epicardial myocytes of the I/R group （P〈0.05）. SpostC prolonged APD and increased peak Ica, L densities in epicardial myocytes exposed to I/R injury （P〈0.05）. SpostC decreased intracellular reactive oxygen species （ROS） levels, reduced the incidence of ventricular tachycardia and ventricular fibrillation, and decreased reperfusion arrhythmia scores compared with the I/R group （all P〈0.05）. Conclusions SpostC attenuates APD shortening and Ica, L suppression induced by I/R injury. The regulation of APD and lea, L by SpostC might be related with intracellular ROS modulation, which contributes to the alleviation of reperfusion ventricular arrhvthmia.展开更多
Using alginic acid to adsorb polypeptides at pH 2.7, we isolated a peptide pea albumin 1b (PA1b) from pea seeds. The PA1b is a single chain peptide consisting of 37 amino acid residues with 6 cysteines which constitut...Using alginic acid to adsorb polypeptides at pH 2.7, we isolated a peptide pea albumin 1b (PA1b) from pea seeds. The PA1b is a single chain peptide consisting of 37 amino acid residues with 6 cysteines which constitutes the cystine-knot structure. Using microfluorometry and patch clamp techniques, we found that PA1b significantly elevated the intracellular calcium level ([Ca2+ ]i) and elicited membrane capacitance increase in the primary rat pancreatic β cells. The PA1b effect on [Ca2+]i elevation was abolished in the absence of extracellular Ca2+ or in the presence of L-type Ca2+ channel blocker, ni- modipine. Interestingly, we found that PA1b significantly depolarized membrane potential, which could lead to the opening of voltage-dependent L-type Ca2+ channels and influx of extracellular Ca2+, and then evoke robust secretion. In this study we identified the plant peptide PA1b which is capable of affecting the excitability and function of mammalian pancreatic β cell.展开更多
基金supported by the National Key Research&Development Program of China(2022YFC3602700 and 2022YFC3602702)the Science and Technology Innovation 2030—Brain Science and Brain-Inspired Intelligence Project(2021ZD0201301)+5 种基金the National Natural Science Foundation of China(32170688,31971159,and 12034015)the Innovation Program of Shanghai Municipal Education Commission(2019-01-07-00-07-E00041)the Shanghai Municipal Science and Technology Major Project(2018SHZDZX01)the ZJ Labthe Shanghai Center for Brain Science and Brain-Inspired Technology,the Program of Shanghai Academic Research Leaders(21XD1403600)the Fundamental Research Funds for the Central Universities(22120230562).
文摘As a noninvasive technique,ultrasound stimulation is known to modulate neuronal activity both in vitro and in vivo.The latest explanation of this phenomenon is that the acoustic wave can activate the ion channels and further impact the electrophysiological properties of targeted neurons.However,the underlying mechanism of low-intensity pulsed ultrasound(LIPUS)-induced neuro-modulation effects is still unclear.Here,we characterize the excitatory effects of LIPUS on spontaneous activity and the intracellular Ca^(2+)homeostasis in cultured hippocampal neurons.By whole-cell patch clamp recording,we found that 15 min of 1-MHz LIPUS boosts the frequency of both spontaneous action potentials and spontaneous excitatory synaptic currents(sEPSCs)and also increases the amplitude of sEPSCs in hippocampal neurons.This phenomenon lasts for>10 min after LIPUS exposure.Together with Ca^(2+)imaging,we clarified that LIPUS increases the[Ca^(2+)]cyto level by facilitating L-type Ca^(2+)channels(LTCCs).In addition,due to the[Ca^(2+)]cyto elevation by LIPUS exposure,the Ca^(2+)-dependent CaMKII-CREB pathway can be activated within 30 min to further regulate the gene transcription and protein expression.Our work suggests that LIPUS regulates neuronal activity in a Ca^(2+)-dependent manner via LTCCs.This may also explain the multi-activation effects of LIPUS beyond neurons.LIPUS stimulation potentiates spontaneous neuronal activity by increasing Ca^(2+)influx.
基金China Postdoctoral Science Foundation (No.20090461048)Postdoctoral Science Foundation of Jiangsu Province (No.0901022C)Postdoctoral Science Foundation of Southeast University
文摘The characteristic impedances of L-type and T-type networks are first investigated for a distributed amplifier design.The analysis shows that the L-type network has better frequency characteristics than the T-type one.A distribution amplifier based on the L-type network is implemented with the 2-μm GaAs HBT（heterojunction-bipolar transistor） process of WIN semiconductors.The measurement result presents excellent bandwidth performance and gives a gain of 5.5 dB with a gain flatness of ±1dB over a frequency range from 3 to 18 GHz.The return losses S11 and S22 are below-10dB in the designed frequency range.The output 1-dB compression point at 5 GHz is 13.3 dBm.The chip area is 0.95 mm2 and the power dissipation is 95 mW under a 3.5 V supply.
基金Chongqing Municipal Commission of Health and Family Planning(Grant No.2015ZBXM005)
文摘In the present study, we aimed to evaluate the effects of cilnidipine and L-type calcium channel blockers（L-type CCBs） on renal function in hypertensive patients. The randomized controlled trials（RCTs） of cilnidipine and L-type CCBs on hypertension treatment were selected from Pubmed, Embase, Google Scholar, CNKI, Science Direct, Ebsco, Springer, Ovid, Cochrane Library, Medline, VIP and Wanfang databases（from the date of databases＇ establishment to September 2014）. Data were independently evaluated following the Jadad standard. The percentage changes of serum creatinine（SCr） value, urinary protein excretion（UPE）, urinary protein/creatinine ratio（UPCR） and estimated glomerular filtration rate（e GFR） pre- and post-treatment were extracted for the subsequent meta-analysis. The mean difference（MD） and the 95% confidence interval（95% CI） were determined using RevM an 5.3 software. A total of 10 RCTs of high quality were included and analyzed by fixedor random-effect models. The results indicated that UPE（MD = –36.59, 95% CI： –70.85, –2.33） or UPCR（MD = –46.56, 95% CI： –88.50, –4.62） was significantly reduced by cilnidipine compared with L-type CCBs. However, such significant difference was not detected in reduction of SCr（MD = 0.01, 95% CI： –2.97, 2.98） or eG FR（MD = 1.56, 95% CI： –0.19, 3.31）. Compared with L-type CCBs, cilnidipine was more effective in reducing proteinuria or preventing the proteinuria progression. In addition, we did not find significant differences in SCr and eG FR between the two groups.
基金supported by grants from the National Natural Science Foundation of China(81671249)the Natural Science Foundation of Shandong Province,China(ZR2016CM04).
文摘In the present study,we investigated the mechanisms underlying the mediation of iron transport by Ltype Ca^2+ channels(LTCCs)in primary cultured ventral mesencephalon(VM)neurons from rats.We found that cotreatment with 100 lmol/L FeSO4 and MPP^+(1-methyl-4-phenylpyridinium)significantly increased the production of intracellular reactive oxygen species,decreased the mitochondrial transmembrane potential and increased the caspase-3 activation compared to MPP^+ treatment alone.Co-treatment with 500 lmol/L CaCl2 further aggravated the FeSO4-induced neurotoxicity in MPP^+-treated VM neurons.Co-treatment with 10 lmol/L isradipine,an LTCC blocker,alleviated the neurotoxicity induced by co-application of FeSO4 and FeSO4/CaCl2.Further studies indicated that MPP^+treatment accelerated the iron influx into VM neurons.In addition,FeSO4 treatment significantly increased the intracellular Ca^2+ concentration.These effects were blocked by isradipine.These results suggest that elevated extracellular Ca^2+ aggravates ironinduced neurotoxicity.LTCCs mediate iron transport in dopaminergic neurons and this,in turn,results in elevated intracellular Ca^2+ and further aggravates iron-induced neurotoxicity.
基金Foundation item： Supported by the National Natural Science Foundation of China （Grant Nos. 41176074, 51379043 and 51409063）Acknowledgement This project was supported by the National Natural Science Foundation of China （Grant Nos. 41176074,51379043 and 51409063） and was conducted in response to the great support received from a basic research project entitled ＂Multihull Ship Technology Key Laboratory of Fundamental Science for National Defence＂, which was conducted at Harbin Engineering University. The authors would like to extend their sincere gratitude to their colleagues in the towing tank laboratory.
文摘Experimental tests were conducted to evaluate the hydrodynamic performance of an L-type podded propulsor in straight-ahead motion and off-design conditions using an open-water measuring instrument developed by the authors for podded propulsors, a ship model towing tank, and under water particle image velocimetry （PIV） measurement systems. Under the three types of conditions, the main parameters of an L-type podded propulsor were measured, including the propeller thrust and torque, as well as the thrust, side force, and moment of the whole pod unit.In addition, the flow field on the section between the propeller and the strut was analyzed. Experimental results demonstrate that the dynamic azimuthing rate and direction and the turning direction affect the forces on the propeller and the whole pod unit. Forces are asymmetrically distributed between the left and right azimuthing directions because of the effect of propeller rotation. The findings of this study provide a foundation for further research on L-type podded propulsors.
基金This research project was supported by Mahidol University,Thailand.We also thank the Faculty of Medicine Siriraj Hospital,Mahidol University,for additional financial support to K.R.and W.B.W。
文摘Objective To investigate the effect of ferulic acid,a natural compound,on pancreatic beta cell viability,Ca^(2+)channels,and insulin secretion.Methods We studied the effects of ferulic acid on rat insulinoma cell line viability using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide viability assay.The whole-cell patch-clamp technique and enzyme-linked immunosorbent assay were also used to examine the action of ferulic acid on Ca^(2+)channels and insulin secretion,respectively.Results Ferulic acid did not affect cell viability during exposures up to 72 h.The electrophysiological study demonstrated that ferulic acid rapidly and concentration-dependently increased L-type Ca^(2+)channel current,shifting its activation curve in the hyperpolarizing direction with a decreased slope factor,while the voltage dependence of inactivation was not affected.On the other hand,ferulic acid have no effect on T-type Ca^(2+)channels.Furthermore,ferulic acid significantly increased insulin secretion,an effect inhibited by nifedipine and Ca^(2+)-free extracellular fluid,confirming that ferulic acid-induced insulin secretion in these cells was mediated by augmenting Ca^(2+)influx through L-type Ca^(2+)channel.Our data also suggest that this may be a direct,nongenomic action.Conclusion This is the first electrophysiological demonstration that acute ferulic acid treatment could increase L-type Ca^(2+)channel current in pancreaticβcells by enhancing its voltage dependence of activation,leading to insulin secretion.
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.
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.
文摘Sigma-1 receptors are unique receptors that are postulated to act as intracellular amplifiers for signal transduction within cells of the nervous system. The present paper studied the
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Objectives Heart failure （HF） is one of the most common outcome for all kinds of heart diseases, the effects of energetic therapy on HF remains controversial, especially to ischemic HF. The aim of this study was to explore the effect of exogenous phosphocreatine with different concentration on L-type calcium（I Cc-L） current in ischemic ventricular myocytes of guinea pig and to investigate its underlying electrophysiological mechanism for the treatment of ischemic HF. Methods Single ventricular myocytes were isolated enzymatically from left ventricle of guinea pig. Peak I Ca-L current were recorded using patch clamp techniques in the whole-cell configuration when myocytes had been superfused with normal Tyrode solution, simple ischemic solution, ischemic solution containing phosphocreatine with different concentration for 10 minutes respectively. Results Peak I Ca-L current density of myocytes superfused with simple simulated ischemic solution was remarkably inhibited by 80.6 ± 5.2% compared with myocytes superfused with normal Tyrode solution（P〈0.05）. Ischemic solution containing phosphocreatine of 5, 10, 20, 30mmol/L inhibited Peak I Ca-L current density by （53.8±6.7）%, （41.8 ± 8.2）%, （38.1±7.4）%, （36.6±9.7）% respectively. There was no statistical significance among phosphocreation of 10, 20, 30 mmol / L. Conclusions Extrogenous phosphocreatine could reverse the inhibition of I Ca-L current under ischemic condition, which could be the ionic basis for the treatment of ischemic heart failure. 0-10 mmol/L phosphocreatine exerted significant dose-effect relationship which no longer existed as concentration more than 10 mmol/L. It is supposed that phosphocreatine increased I Ca-L current by many pathways rather than simple substrate for ATP synthesis.
基金Supported by National Research Council of Thailand Thesis Grant for Doctoral Degree Student and the Siriraj Graduate Scholarship(both to K.T.)the Faculty of Medicine Siriraj Hospital,Mahidol University(to W.B.W.and K.R.)。
文摘Objective:To study hesperetin-induced vasorelaxation after depolarizing contraction in human umbilical veins(HUVs)to elucidate the role of L-type Ca^(2+)channel(LTCC)and related signaling pathway.Methods:Isometric tension recording was performed in HUV rings pre-contracted with K^(+).Hesperetin relaxing mechanism was investigated using a LTCC opener(BayK8644)and blockers of cyclic nucleotides and phosphodiesterases(PDEs).Whole-cell patch-clamping in A7r5 cells,a rat vascular smooth muscle cell line,was performed to study the effect of hesperetin on LTCC current.Results:After depolarizing precontraction,hesperetin induced HUV relaxation concentration-dependently and endothelium-independently;1 mmol/L hesperetin reduced denuded HUV ring tension by 68.7%±4.3%compared to matching vehicle,osmolality,and time controls(P<0.0001).Importantly,hesperetin competitively inhibited BayK8644-induced contraction,shifting the half maximal effective concentration of BayK8644 response from 1.08 nmol/L[95%confidence interval(CI)0.49-2.40]in vehicle control to11.30 nmol/L(95%CI 5.45-23.41)in hesperetin(P=0.0001).Moreover,hesperetin elicited further vasorelaxation in denuded HUV rings pretreated with inhibitors of soluble guanylyl cyclase,adenylyl cyclase,PDE3,PDE4,and PDE5(P<0.01),while rings pretreated with PDE1 inhibitors could not be relaxed by hesperetin(P>0.05).However,simultaneously applying inhibitors of soluble guanylyl cyclase and adenylyl cyclase could not inhibit hesperetin's effect(P>0.05).In whole-cell patch-clamping,hesperetin rapidly decreased LTCC current in A7r5 cells to66.7%±5.8%(P=0.0104).Conclusions:Hesperetin diminishes depolarizing contraction of human vascular smooth muscle through inhibition of LTCC,and not cyclic nucleotides nor PDEs.Our evidence supports direct LTCC interaction and provides additional basis for the use of hesperetin and its precursor hesperidin as vasodilators and may lead to future vasodilator drug development as a treatment alternative for cardiovascular diseases.
基金This work was supported by the grant Irom the National Natural Science Foundation of China （No. 81070098） and Foundation for Postgraduates＇ Innovative Research of Peking Union Medical College （No. 2010-1002-004）.
文摘Background It has been proved that sevoflurane postconditioning （SpostC） could protect the heart against myocardial ischemia/reperfusion injury, however, there has been few research focused on the electrophysiological effects of SpostC. The objective of the study was to investigate the effects of SpostC on action potential duration （APD） and L-type calcium current （Ica, L） in isolated cardiomyocytes. Methods Langendorff perfused SD rat hearts were randomly assigned to one of the time control （TC）, ischemia/reperfusion （I/R, 25 minutes of ischemia followed by 30 minutes of reperfusion）, and SpostC （postconditioned with 3% sevoflurane） groups. At the end of reperfusion, epicardial myocytes were dissociated enzymatically for patch clamp studies. Results Sevoflurane directly prolonged APD and decreased peak Ica, L densities in epicardial myocytes of the TC group （P〈0.05）. I/R injury shortened APD and decreased peak Ica, L densities in epicardial myocytes of the I/R group （P〈0.05）. SpostC prolonged APD and increased peak Ica, L densities in epicardial myocytes exposed to I/R injury （P〈0.05）. SpostC decreased intracellular reactive oxygen species （ROS） levels, reduced the incidence of ventricular tachycardia and ventricular fibrillation, and decreased reperfusion arrhythmia scores compared with the I/R group （all P〈0.05）. Conclusions SpostC attenuates APD shortening and Ica, L suppression induced by I/R injury. The regulation of APD and lea, L by SpostC might be related with intracellular ROS modulation, which contributes to the alleviation of reperfusion ventricular arrhvthmia.
基金the National Natural Science Foundation of China (Grant Nos. 30370674,30470448, and 30470646)the CAS Project (Grant No. KSCX2-SW-224)+1 种基金the China "863" Program (Grant No. 2012AA214066)The laboratory of Tao Xu is also supported by the Partner Group Scheme of the Max Planck Institute for Bio-physical Chemistry, Gttingen
文摘Using alginic acid to adsorb polypeptides at pH 2.7, we isolated a peptide pea albumin 1b (PA1b) from pea seeds. The PA1b is a single chain peptide consisting of 37 amino acid residues with 6 cysteines which constitutes the cystine-knot structure. Using microfluorometry and patch clamp techniques, we found that PA1b significantly elevated the intracellular calcium level ([Ca2+ ]i) and elicited membrane capacitance increase in the primary rat pancreatic β cells. The PA1b effect on [Ca2+]i elevation was abolished in the absence of extracellular Ca2+ or in the presence of L-type Ca2+ channel blocker, ni- modipine. Interestingly, we found that PA1b significantly depolarized membrane potential, which could lead to the opening of voltage-dependent L-type Ca2+ channels and influx of extracellular Ca2+, and then evoke robust secretion. In this study we identified the plant peptide PA1b which is capable of affecting the excitability and function of mammalian pancreatic β cell.
