Objective：To study the effects of sodium ferulate on the ultrarapid delayed rectifier K^＋ current（IKur） in human atrial myocytes. Methods：Human atrial myocytes were isolated by enzyme dispersion method. IKur, in ...Objective：To study the effects of sodium ferulate on the ultrarapid delayed rectifier K^＋ current（IKur） in human atrial myocytes. Methods：Human atrial myocytes were isolated by enzyme dispersion method. IKur, in human atrial myocytes were recorded by using the whole cell patch clamp. The changes of IKur were compared in the absence and the presence of sodium ferulate. Results：There was no effect of 0.4 g/L sodium ferulate on I-V relation of IKur. However, 0.4 g/L sodium ferulate inhibited IKur to some degrees at each test pulse. The current densities of IKur at ＋60 mV decreased from 4.997 ± 0.35 PA/PF to 3.331 ± 0.26 PA/PF（n = 6, P 〈 0.05）. The inhibitory effect was concentration-dependent. IC50 was（0.41 ±0.03）g/L and the Hill coefficient was 0.95 ± 0.05. Conclusion：Sodium ferulate as a potassium channel blocker can inhibit IKur in human atrial myocytes effectively.展开更多
The study examined the inhibitory effect of Atractylodes macrocephala （AM） on the uterine contraction during premature delivery and explored its electrophysiological mechanism by studying the effects of AM on the C...The study examined the inhibitory effect of Atractylodes macrocephala （AM） on the uterine contraction during premature delivery and explored its electrophysiological mechanism by studying the effects of AM on the Ca^2＋-activated K^＋ currents of pregnant human myometrial smooth muscle cells with or without the treatment with intedeukin-6. Single cells were acutely isolated from pregnant human myometrial smooth muscles. Whole-cell Ca^2＋-activated K^＋ currents were recorded by using an Axopatchl-D amplifier. The cells were divided into three groups： group A in which AM was added into perfusate, group B, in which interleukin-6 was added into perfusate） and group C in which AM was added into perfusate after addition of interleukin-6. IL-6 10 ng/mL inhibited BKca by 36.9%±13.7% as compared with control （P〈0.01）. AM at 2 mg/mL raised BKca by 36.7%±22.6% or 45.2%±13.7% with or without the treatment of IL-6, respectively （P〈0.01）. It is concluded that AM was able to enhance the BKca of pregnant human myometrial smooth muscle cells treated or untreated with interleukin-6 and its effect on the BKca IL-treated cells was stronger that its effect on BKca of untreated cells. Our results suggested that AM can help to maintain the membrane potentials and the resting status of pregnant human myometrial smooth muscle cells.展开更多
We used whole-vacuolar patch-clamp recording mode to study the action mechanism of La3+ to Slow Vacuolar (SV) channels for the first time. We recorded SV channel currents of Xinlimei (Raphanus satirus L.) vacuolars. T...We used whole-vacuolar patch-clamp recording mode to study the action mechanism of La3+ to Slow Vacuolar (SV) channels for the first time. We recorded SV channel currents of Xinlimei (Raphanus satirus L.) vacuolars. The minimum activation potentials of voltage-dependent SV channels tied in 25+/-5 mV. The increase in cytoplasmic Ca2+ led to enhancement of SV-type currents. It was found that the threshold potential of activation shifted towards more depolarized values whenever cytoplasmic Ca2+ was increased. When 10(-10) mol/L free La3+ was added to the bath, SV-type current was suppressed by 60 similar to 75%. These data showed La3+ reduced ion permeabilities of Xinlimei root vacuolar membrane.展开更多
The protective effect of carvedilol on abnormality of L-type calcium current induced by oxygen free radical in single guinea pig ventricular myocytes was studied. Whole-cell patch clamp technique was used to study the...The protective effect of carvedilol on abnormality of L-type calcium current induced by oxygen free radical in single guinea pig ventricular myocytes was studied. Whole-cell patch clamp technique was used to study the effect of H 2O 2 (0.5 mmol/L) on L-type calcium current in single guinea pig ventricular myocytes and the action of pretreatment with carvedilol (0.5 μmol/L). 0.5 μmol/L carvedilol had no significant effect on I Ca,L and its channel dynamics. In the presence of 0.5 mmol/L H 2O 2, peak current of I Ca,L was reduced significantly (P<0.001), the I-V curve of I Ca,L was shifted upward, steady-state activation curve and steady-state deactivation curve of I Ca,L were shifted left and recovery time of I Ca,L was delayed significantly (P<0.001). 0.5 μmol/L carvedilol significantly alleviated the inhibitory effect of H 2O 2 on I Ca,L as compared with that in H 2O 2 group (P<0.01). In addition, carvedilol reversed the changes of dynamics of I Ca,L induced by H 2O 2. It was concluded that carvedilol could alleviate the abnormality of L-type calcium current induced by oxygen free radical in cardiomyocytes. It shows partly the possible mechanism of the special availability of carvedilol in chronic heart failure.展开更多
To elucidate the mechanism of arrhythmia in healed myocardial infarction (HMI), the changes of action potential duration (APD), transient outward potassium current (I to), delayed rectifier potassium current (I K)...To elucidate the mechanism of arrhythmia in healed myocardial infarction (HMI), the changes of action potential duration (APD), transient outward potassium current (I to), delayed rectifier potassium current (I K) and inward rectifier potassium current (I K1) of left ventricular myocytes in non-infarcted zone of HMI were investigated. Rabbits were randomly assigned into two groups: HMI group, in which animals were subjected to thoracotomy and ligation of the circumflex coronary and sham-operated group, in which rabbits underwent thoracotomy but no conorary ligation. 3 months after the operation, the whole myocyte patch clamp technique was used to record APD, I to, I K, and I K1 of ventricular myocytes in non-infarcted zone.Our results showed that the membrane capacitance was larger in HMI group than in sham-operated group. Action potential duration was significantly lengthened in HMI group and early afterdepolarization (EAD) appeared in HMI group. The densities of I to, I K, tail, and I K1 were reduced significantly in HMI group, from 6.72±0.42 pA/pF, 1.54±0.13 pA/pF and 25.6±2.6 pA/pF in sham-operated group to 4.03±0.33 pA/pF, 1.14±0.11 pA/pF and 17.6 ±2.3 pA/pF, respectively. It is concluded that the reduced densities of I to , I K, tail and I K1 in ventricular myocytes of non-infarcted zone in HMI were responsible for the prolongation of APD and the presentation of EAD which played important roles in the development of malignant arrhythmia in HMI.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
Many rat taste receptor cells conduct action potentials(APs).APs had a mean threshold of -35 mV(n=95 cells)and a spike height of 52mV above threshold in current clamp(hold= -80mV).Aps could be classified into two sign...Many rat taste receptor cells conduct action potentials(APs).APs had a mean threshold of -35 mV(n=95 cells)and a spike height of 52mV above threshold in current clamp(hold= -80mV).Aps could be classified into two significantly different (P<0.001) groups-fast,with short half-time durations and large outward currents (mean1.3 ms and 2.7nA),and slow,with long duration and small outward currents(mean9.2ms and 0. 29nA).AP upstrokes were conducted by TTX-sensitive sodium currents whereas the downstroke by TEA-blockable outward currents. Voltage dependent analysis of outward current separated transient and sustained components.The transient component was specifically blocked by 4-AP(1mmol/L).A calcium-dependent outward component was also revealed modulating voltage and external calcium concentration.The fast recovery phase of the AP appears related the sustained outward current whereas the after hyperpolarization(AHP) was blocked by 4AP suggesting a significant contribution of the transient component.Forskolin (FSK),which elevates cAMP,reversibly blocked the majority of the sustained current without influencing the transient. FSK greatly exaggerated the AHP without changing the spike height or duration. These data suggest that several components of the outward current contribute specifically to the gustatory AP and that the AP may be modulated by cyclic nucleotides.展开更多
Objectives To investigate effect of Angll, captopril on single guinea myocytes on L - type calcium current and sodium current. Methods Membrane patch clamp whole cell recording technique was used to investigate effect...Objectives To investigate effect of Angll, captopril on single guinea myocytes on L - type calcium current and sodium current. Methods Membrane patch clamp whole cell recording technique was used to investigate effect of angll, captopril on L - Ca maximum current density and sodium maximum current density. Resutls Angll increased the maximum current density compared with control after perfused 5 min, 357. 7 ±219. 7 Vs 279. 5± 240. 5 PA/PF, increase rate is 27. 9 %, the shape of current - voltage relationship curve was unchanged, peaked at + 10 mv, indicated that angll increased L - Ca current density in voltage - dependent. After perfused with captopril, captopril + angll 3, 5 min, L - Ca current was recorded, results suggest L - Ca maximum current density decreased significantly compared with control, in captopril group, 128. 4 ± 92. 6Vs286. 2 ± 89. 7, 66. 7±68. 3Vs 286. 2 ± 89. 7, respectively, rate of inhibition is 55. 1 %, 76. 6 %, respectively. L - Ca current further decreased in captopril perfused 5 min compared with 3 min, 66. 7 ± 68. 3 Vs 128. 4 ± 92. 6, in captopril + angll group, L - Ca current decreased greatly in 3, 5 min than control, 143. 4±117. 6Vs 267. 7±141. 4, 96. 4±82. 5 Vs 267. 7±141. 4, respectively, rate of inhibition is 46. 4 % , 63. 9 % respectively. We also investigated effect of captopril on Na current, which decreased significantly in 1 min and 3 min compared with control, 939. 1 ±319. 1 Vs 1398. 0±144. 6 PA/PF, 469. 95 ± 314. 9 Vs 1398. 0 ±144. 6 PA/PF, respectively, rate of inhibition is 32. 8 % , 66. 3 % , respectively. Na current density decreased significantly in 3 min compared with 1 min, 469. 9±314. 9 Vs 939. 1±319. 1PA/PF, rate of inhibition is 49. 9 % . Conclusions Angiotensin Ⅱexerts increased maximum current density of L - Ca in voltage dependent, captopril decreased maximum current density of L - Ca in voltage dependent, decreased sodium maximum current density, which is the prominently antiarrhythmia mechanisms through inhibition of angiotensin Ⅱ evoked calcium dependent transient inward current and calcium overload.展开更多
Background Allitridi is an active compound that is extracted from the garlic. It has effects of anti-atherosclerosis, anti-arrhythmias and lowering blood pressure. But the controversy about the effect on cardiac contr...Background Allitridi is an active compound that is extracted from the garlic. It has effects of anti-atherosclerosis, anti-arrhythmias and lowering blood pressure. But the controversy about the effect on cardiac contractility still exists. Methods Whole-cell patch clamp recording technique was used to record ICa,Lin single cell isolated rat ventricular myocytes. The nifedipine- sensitive L-type calcium current was recorded in the rat ventricular myocytes. Results Allitridi decreased the calcium channel current in a dose-dependent and voltage-dependent manner in ventricular myocytes of rats. The current-voltage curve was shifted upwards, on which active potential,peak potential and reverse potential showed no significant changes. The inactivation curve was shifted to more negative potential, but the activation curve and recovery curve were not altered. Allitridi had no effect on frequent-dependency of calcium current. Conclusion These results show that allitridi could concentration-dependently decrease calcium channel current in ventricular myocytes of rats.展开更多
The current difference between male and female rabbit ventricular myocytes was investigated for elucidating the mechanism of longer QT interval and higher incidence of drug-associated torsade de pointes in female rabb...The current difference between male and female rabbit ventricular myocytes was investigated for elucidating the mechanism of longer QT interval and higher incidence of drug-associated torsade de pointes in female rabbits than in male rabbits. Whole cell patch clamp technique was used to record APD, I_to, I_K,tail, I_K1 and I_Ca,L of myocytes from left ventricular apex. There was no difference in the membrane capacitance between male and female rabbit myocytes. APD_90 was longer in female rabbits (560.4±26.5 ms, n=15) than in male ones (489.0±20.7 ms, n=14), P<0.05. In female rabbit myocytes, I_K,tail, I_to, I_K1 and I_Ca,L were 0.71±0.05 pA/pF (n=17), 8.28±1.03 pA/pF (n=18), 24.5±3.6 pA/pF (n=12) and 9.0±2.3 pA/pF (n=15) respectively. In male rabbit myocytes, they were 0.84±0.07 pA/pF (n=18), 8.60±1.20 pA/pF (n=18), 25.9±4.5 pA/pF (n=14) and 9.3±2.6 pA/pF (n=16) respectively. I_K,tail in female rabbits was significantly lower than that of male rabbits (P<0.05), but there was no difference in I_to, I_K1 and I_Ca,L between male rabbits and female rabbits (P>0.05). The lower I_K,tail of female rabbit myocytes may contribute to the longer repolarization and the higher incidence of drug-associated torsade de pointes.展开更多
Objectives The effects of carvedilol on sodium current （INa） were investigated in isolated adult rat ventricular myocytes. Methods Single ventricular myocytes were enzymatically dissociated. INa was recorded by whol...Objectives The effects of carvedilol on sodium current （INa） were investigated in isolated adult rat ventricular myocytes. Methods Single ventricular myocytes were enzymatically dissociated. INa was recorded by whole-cell patch- clamp recording technique. Results an IC50of （6. 35 - 0.40） mol . L^- 1. Carvedilol reversibly inhibited INa in a concentration-dependent manner, with 2. This inhibition was voltage- and frequency-dependent. 3. Carvedilol decreased the peak of the I-V relationship curve at -35 mV from （17.31± 1.68） pA/pF to （6. 58 ± 1.35） pA/pF, but did not change active potential, peak potential and the reverse potential significantly. 4. The steady-state inactivation curve of INa was shifted to more negative potentials. Conclusions Carvedilol inhibits INa in adult rat ventricular myocytes by mechanisms involving preferential interaction with the inactivated state of sodium channel.展开更多
Swelling-activated chloride currents（ICl.swell） are thought to play a role in several physiologic and pathophysiologic processes and thus represent a target for therapeutic approaches. However, the mechanism of ICl....Swelling-activated chloride currents（ICl.swell） are thought to play a role in several physiologic and pathophysiologic processes and thus represent a target for therapeutic approaches. However, the mechanism of ICl.swell regulation remains unclear. In this study, we used the whole-cell patch-clamp technique to examine the role of protein kinase C（PKC） in the regulation of ICl.swell in human atrial myocytes. Atrial myocytes were isolated from the right atrial appendages of patients undergoing coronary artery bypass and enzymatically dissociated. ICl.swell was evoked in hypotonic solution and recorded using the whole-cell patch-clamp technique. The PKC agonist phorbol dibutyrate（PDBu） enhanced ICl.swellin a concentration-dependent manner, which was reversed in isotonic solution and by a chloride current inhibitor, 9-anthracenecarboxylicacid. Furthermore, the PKC inhibitor bis-indolylmaleimide attenuated the effect and 4α-PDBu, an inactive PDBu analog, had no effect on ICl.swell. These results, obtained using the whole-cell patch-clamp technique, demonstrate the ability of PKC to activate ICl,swell in human atrial myocytes. This observation was consistent with a previous study using a single-channel patch-clamp technique, but differed from some findings in other species.展开更多
The electrophysiological properties of potassium ion channels are regarded as a basic index for determining the functional differentiation of neural stem cells. In this study, neural stem cells from the hippocampus of...The electrophysiological properties of potassium ion channels are regarded as a basic index for determining the functional differentiation of neural stem cells. In this study, neural stem cells from the hippocampus of newborn rats were induced to differentiate with neurotrophic growth factor, and the electrophysiological properties of the voltage-gated potassium ion channels were observed. Immunofluorescence staining showed that the rapidly proliferating neural stem cells formed spheres in vitro that expressed high levels of nestin. The differentiated neurons were shown to express neuron-specific enolase. Flow cytometric analysis revealed that the neural stem cells were actively dividing and the percentage of cells in the S ＋ G2/M phase was high. However, the ratio of cells in the S ＋ G2/M phase decreased obviously as differentiation proceeded. Whole-cell patch-clamp re- cordings revealed apparent changes in potassium ion currents as the neurons differentiated. The potassium ion currents consisted of one transient outward potassium ion current and one delayed rectifier potassium ion current, which were blocked by 4-aminopyridine and tetraethylammonium, respectively. The experimental findings indicate that neural stem cells from newborn rat hippo- campus could be cultured and induced to differentiate into functional neurons under defined condi- tions in vitro. The differentiated neurons expressed two types of outward potassium ion cur＇ents similar to those of mature neurons in vivo.展开更多
在电池充电中,感应电能传输(inductive power transfer,IPT)系统通常需要实现恒流(constant current,CC)和恒压(constant voltage,CV)输出。同时,IPT系统的线圈偏移是难以避免的,因此系统同时需要具有抗偏移能力。文中提出一种基于混合...在电池充电中,感应电能传输(inductive power transfer,IPT)系统通常需要实现恒流(constant current,CC)和恒压(constant voltage,CV)输出。同时,IPT系统的线圈偏移是难以避免的,因此系统同时需要具有抗偏移能力。文中提出一种基于混合钳位拓扑的IPT系统,利用钳位电路实现CC到CV的自动切换,通过四线圈结构的混合拓扑提高系统的抗偏移性能,简化系统控制复杂性。最后,搭建一个400 W的原理样机,验证所提方法的正确性和有效性。负载在5~100Ω范围变化时,系统在X轴方向偏移达52.5%和Z轴方向偏移为17.5%的情况下,CC模式下的输出电流和CV模式下的输出电压波动始终小于5%。展开更多
基金This work was supported by the National Natural Science Foundation of China(No.30700747)
文摘Objective：To study the effects of sodium ferulate on the ultrarapid delayed rectifier K^＋ current（IKur） in human atrial myocytes. Methods：Human atrial myocytes were isolated by enzyme dispersion method. IKur, in human atrial myocytes were recorded by using the whole cell patch clamp. The changes of IKur were compared in the absence and the presence of sodium ferulate. Results：There was no effect of 0.4 g/L sodium ferulate on I-V relation of IKur. However, 0.4 g/L sodium ferulate inhibited IKur to some degrees at each test pulse. The current densities of IKur at ＋60 mV decreased from 4.997 ± 0.35 PA/PF to 3.331 ± 0.26 PA/PF（n = 6, P 〈 0.05）. The inhibitory effect was concentration-dependent. IC50 was（0.41 ±0.03）g/L and the Hill coefficient was 0.95 ± 0.05. Conclusion：Sodium ferulate as a potassium channel blocker can inhibit IKur in human atrial myocytes effectively.
文摘The study examined the inhibitory effect of Atractylodes macrocephala （AM） on the uterine contraction during premature delivery and explored its electrophysiological mechanism by studying the effects of AM on the Ca^2＋-activated K^＋ currents of pregnant human myometrial smooth muscle cells with or without the treatment with intedeukin-6. Single cells were acutely isolated from pregnant human myometrial smooth muscles. Whole-cell Ca^2＋-activated K^＋ currents were recorded by using an Axopatchl-D amplifier. The cells were divided into three groups： group A in which AM was added into perfusate, group B, in which interleukin-6 was added into perfusate） and group C in which AM was added into perfusate after addition of interleukin-6. IL-6 10 ng/mL inhibited BKca by 36.9%±13.7% as compared with control （P〈0.01）. AM at 2 mg/mL raised BKca by 36.7%±22.6% or 45.2%±13.7% with or without the treatment of IL-6, respectively （P〈0.01）. It is concluded that AM was able to enhance the BKca of pregnant human myometrial smooth muscle cells treated or untreated with interleukin-6 and its effect on the BKca IL-treated cells was stronger that its effect on BKca of untreated cells. Our results suggested that AM can help to maintain the membrane potentials and the resting status of pregnant human myometrial smooth muscle cells.
基金The authors acknowledge the support of the National Natural Science Foundation of ChinaProvincial Natural Science Foundation of Shanxi.
文摘We used whole-vacuolar patch-clamp recording mode to study the action mechanism of La3+ to Slow Vacuolar (SV) channels for the first time. We recorded SV channel currents of Xinlimei (Raphanus satirus L.) vacuolars. The minimum activation potentials of voltage-dependent SV channels tied in 25+/-5 mV. The increase in cytoplasmic Ca2+ led to enhancement of SV-type currents. It was found that the threshold potential of activation shifted towards more depolarized values whenever cytoplasmic Ca2+ was increased. When 10(-10) mol/L free La3+ was added to the bath, SV-type current was suppressed by 60 similar to 75%. These data showed La3+ reduced ion permeabilities of Xinlimei root vacuolar membrane.
文摘The protective effect of carvedilol on abnormality of L-type calcium current induced by oxygen free radical in single guinea pig ventricular myocytes was studied. Whole-cell patch clamp technique was used to study the effect of H 2O 2 (0.5 mmol/L) on L-type calcium current in single guinea pig ventricular myocytes and the action of pretreatment with carvedilol (0.5 μmol/L). 0.5 μmol/L carvedilol had no significant effect on I Ca,L and its channel dynamics. In the presence of 0.5 mmol/L H 2O 2, peak current of I Ca,L was reduced significantly (P<0.001), the I-V curve of I Ca,L was shifted upward, steady-state activation curve and steady-state deactivation curve of I Ca,L were shifted left and recovery time of I Ca,L was delayed significantly (P<0.001). 0.5 μmol/L carvedilol significantly alleviated the inhibitory effect of H 2O 2 on I Ca,L as compared with that in H 2O 2 group (P<0.01). In addition, carvedilol reversed the changes of dynamics of I Ca,L induced by H 2O 2. It was concluded that carvedilol could alleviate the abnormality of L-type calcium current induced by oxygen free radical in cardiomyocytes. It shows partly the possible mechanism of the special availability of carvedilol in chronic heart failure.
文摘To elucidate the mechanism of arrhythmia in healed myocardial infarction (HMI), the changes of action potential duration (APD), transient outward potassium current (I to), delayed rectifier potassium current (I K) and inward rectifier potassium current (I K1) of left ventricular myocytes in non-infarcted zone of HMI were investigated. Rabbits were randomly assigned into two groups: HMI group, in which animals were subjected to thoracotomy and ligation of the circumflex coronary and sham-operated group, in which rabbits underwent thoracotomy but no conorary ligation. 3 months after the operation, the whole myocyte patch clamp technique was used to record APD, I to, I K, and I K1 of ventricular myocytes in non-infarcted zone.Our results showed that the membrane capacitance was larger in HMI group than in sham-operated group. Action potential duration was significantly lengthened in HMI group and early afterdepolarization (EAD) appeared in HMI group. The densities of I to, I K, tail, and I K1 were reduced significantly in HMI group, from 6.72±0.42 pA/pF, 1.54±0.13 pA/pF and 25.6±2.6 pA/pF in sham-operated group to 4.03±0.33 pA/pF, 1.14±0.11 pA/pF and 17.6 ±2.3 pA/pF, respectively. It is concluded that the reduced densities of I to , I K, tail and I K1 in ventricular myocytes of non-infarcted zone in HMI were responsible for the prolongation of APD and the presentation of EAD which played important roles in the development of malignant arrhythmia in HMI.
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.
文摘Many rat taste receptor cells conduct action potentials(APs).APs had a mean threshold of -35 mV(n=95 cells)and a spike height of 52mV above threshold in current clamp(hold= -80mV).Aps could be classified into two significantly different (P<0.001) groups-fast,with short half-time durations and large outward currents (mean1.3 ms and 2.7nA),and slow,with long duration and small outward currents(mean9.2ms and 0. 29nA).AP upstrokes were conducted by TTX-sensitive sodium currents whereas the downstroke by TEA-blockable outward currents. Voltage dependent analysis of outward current separated transient and sustained components.The transient component was specifically blocked by 4-AP(1mmol/L).A calcium-dependent outward component was also revealed modulating voltage and external calcium concentration.The fast recovery phase of the AP appears related the sustained outward current whereas the after hyperpolarization(AHP) was blocked by 4AP suggesting a significant contribution of the transient component.Forskolin (FSK),which elevates cAMP,reversibly blocked the majority of the sustained current without influencing the transient. FSK greatly exaggerated the AHP without changing the spike height or duration. These data suggest that several components of the outward current contribute specifically to the gustatory AP and that the AP may be modulated by cyclic nucleotides.
文摘Objectives To investigate effect of Angll, captopril on single guinea myocytes on L - type calcium current and sodium current. Methods Membrane patch clamp whole cell recording technique was used to investigate effect of angll, captopril on L - Ca maximum current density and sodium maximum current density. Resutls Angll increased the maximum current density compared with control after perfused 5 min, 357. 7 ±219. 7 Vs 279. 5± 240. 5 PA/PF, increase rate is 27. 9 %, the shape of current - voltage relationship curve was unchanged, peaked at + 10 mv, indicated that angll increased L - Ca current density in voltage - dependent. After perfused with captopril, captopril + angll 3, 5 min, L - Ca current was recorded, results suggest L - Ca maximum current density decreased significantly compared with control, in captopril group, 128. 4 ± 92. 6Vs286. 2 ± 89. 7, 66. 7±68. 3Vs 286. 2 ± 89. 7, respectively, rate of inhibition is 55. 1 %, 76. 6 %, respectively. L - Ca current further decreased in captopril perfused 5 min compared with 3 min, 66. 7 ± 68. 3 Vs 128. 4 ± 92. 6, in captopril + angll group, L - Ca current decreased greatly in 3, 5 min than control, 143. 4±117. 6Vs 267. 7±141. 4, 96. 4±82. 5 Vs 267. 7±141. 4, respectively, rate of inhibition is 46. 4 % , 63. 9 % respectively. We also investigated effect of captopril on Na current, which decreased significantly in 1 min and 3 min compared with control, 939. 1 ±319. 1 Vs 1398. 0±144. 6 PA/PF, 469. 95 ± 314. 9 Vs 1398. 0 ±144. 6 PA/PF, respectively, rate of inhibition is 32. 8 % , 66. 3 % , respectively. Na current density decreased significantly in 3 min compared with 1 min, 469. 9±314. 9 Vs 939. 1±319. 1PA/PF, rate of inhibition is 49. 9 % . Conclusions Angiotensin Ⅱexerts increased maximum current density of L - Ca in voltage dependent, captopril decreased maximum current density of L - Ca in voltage dependent, decreased sodium maximum current density, which is the prominently antiarrhythmia mechanisms through inhibition of angiotensin Ⅱ evoked calcium dependent transient inward current and calcium overload.
基金supported by the National Natural Science Foundation of China(No.81273516/No.81270222/No.81302779)Guangdong Provincial Natural Science Foundation(No.S2013010014762/No.S2013040014689)Guangdong Provincial Medical Science Foundation(No.A2011005/No.A2012006)
文摘Background Allitridi is an active compound that is extracted from the garlic. It has effects of anti-atherosclerosis, anti-arrhythmias and lowering blood pressure. But the controversy about the effect on cardiac contractility still exists. Methods Whole-cell patch clamp recording technique was used to record ICa,Lin single cell isolated rat ventricular myocytes. The nifedipine- sensitive L-type calcium current was recorded in the rat ventricular myocytes. Results Allitridi decreased the calcium channel current in a dose-dependent and voltage-dependent manner in ventricular myocytes of rats. The current-voltage curve was shifted upwards, on which active potential,peak potential and reverse potential showed no significant changes. The inactivation curve was shifted to more negative potential, but the activation curve and recovery curve were not altered. Allitridi had no effect on frequent-dependency of calcium current. Conclusion These results show that allitridi could concentration-dependently decrease calcium channel current in ventricular myocytes of rats.
文摘The current difference between male and female rabbit ventricular myocytes was investigated for elucidating the mechanism of longer QT interval and higher incidence of drug-associated torsade de pointes in female rabbits than in male rabbits. Whole cell patch clamp technique was used to record APD, I_to, I_K,tail, I_K1 and I_Ca,L of myocytes from left ventricular apex. There was no difference in the membrane capacitance between male and female rabbit myocytes. APD_90 was longer in female rabbits (560.4±26.5 ms, n=15) than in male ones (489.0±20.7 ms, n=14), P<0.05. In female rabbit myocytes, I_K,tail, I_to, I_K1 and I_Ca,L were 0.71±0.05 pA/pF (n=17), 8.28±1.03 pA/pF (n=18), 24.5±3.6 pA/pF (n=12) and 9.0±2.3 pA/pF (n=15) respectively. In male rabbit myocytes, they were 0.84±0.07 pA/pF (n=18), 8.60±1.20 pA/pF (n=18), 25.9±4.5 pA/pF (n=14) and 9.3±2.6 pA/pF (n=16) respectively. I_K,tail in female rabbits was significantly lower than that of male rabbits (P<0.05), but there was no difference in I_to, I_K1 and I_Ca,L between male rabbits and female rabbits (P>0.05). The lower I_K,tail of female rabbit myocytes may contribute to the longer repolarization and the higher incidence of drug-associated torsade de pointes.
基金supported by Guangdong Provincial Chinese Traditional Medicine Administration Foundation(2060033)Guangdong Provincial Medical Science and Technology Foundation (A2006002)
文摘Objectives The effects of carvedilol on sodium current （INa） were investigated in isolated adult rat ventricular myocytes. Methods Single ventricular myocytes were enzymatically dissociated. INa was recorded by whole-cell patch- clamp recording technique. Results an IC50of （6. 35 - 0.40） mol . L^- 1. Carvedilol reversibly inhibited INa in a concentration-dependent manner, with 2. This inhibition was voltage- and frequency-dependent. 3. Carvedilol decreased the peak of the I-V relationship curve at -35 mV from （17.31± 1.68） pA/pF to （6. 58 ± 1.35） pA/pF, but did not change active potential, peak potential and the reverse potential significantly. 4. The steady-state inactivation curve of INa was shifted to more negative potentials. Conclusions Carvedilol inhibits INa in adult rat ventricular myocytes by mechanisms involving preferential interaction with the inactivated state of sodium channel.
基金supported by grants from the Scientific Research Foundation for Returned Scholars,Ministry of Education of China(No.2004-527)the Project on Social Development,Department of Science and Technology of Guizhou Province,China(No.2011-040)
文摘Swelling-activated chloride currents（ICl.swell） are thought to play a role in several physiologic and pathophysiologic processes and thus represent a target for therapeutic approaches. However, the mechanism of ICl.swell regulation remains unclear. In this study, we used the whole-cell patch-clamp technique to examine the role of protein kinase C（PKC） in the regulation of ICl.swell in human atrial myocytes. Atrial myocytes were isolated from the right atrial appendages of patients undergoing coronary artery bypass and enzymatically dissociated. ICl.swell was evoked in hypotonic solution and recorded using the whole-cell patch-clamp technique. The PKC agonist phorbol dibutyrate（PDBu） enhanced ICl.swellin a concentration-dependent manner, which was reversed in isotonic solution and by a chloride current inhibitor, 9-anthracenecarboxylicacid. Furthermore, the PKC inhibitor bis-indolylmaleimide attenuated the effect and 4α-PDBu, an inactive PDBu analog, had no effect on ICl.swell. These results, obtained using the whole-cell patch-clamp technique, demonstrate the ability of PKC to activate ICl,swell in human atrial myocytes. This observation was consistent with a previous study using a single-channel patch-clamp technique, but differed from some findings in other species.
基金supported by the National Natural Science Foundation of China,No.31000514the Scientific Research Project for Talent with High Education of Xinxiang Medical University,No.2007502002
文摘The electrophysiological properties of potassium ion channels are regarded as a basic index for determining the functional differentiation of neural stem cells. In this study, neural stem cells from the hippocampus of newborn rats were induced to differentiate with neurotrophic growth factor, and the electrophysiological properties of the voltage-gated potassium ion channels were observed. Immunofluorescence staining showed that the rapidly proliferating neural stem cells formed spheres in vitro that expressed high levels of nestin. The differentiated neurons were shown to express neuron-specific enolase. Flow cytometric analysis revealed that the neural stem cells were actively dividing and the percentage of cells in the S ＋ G2/M phase was high. However, the ratio of cells in the S ＋ G2/M phase decreased obviously as differentiation proceeded. Whole-cell patch-clamp re- cordings revealed apparent changes in potassium ion currents as the neurons differentiated. The potassium ion currents consisted of one transient outward potassium ion current and one delayed rectifier potassium ion current, which were blocked by 4-aminopyridine and tetraethylammonium, respectively. The experimental findings indicate that neural stem cells from newborn rat hippo- campus could be cultured and induced to differentiate into functional neurons under defined condi- tions in vitro. The differentiated neurons expressed two types of outward potassium ion cur＇ents similar to those of mature neurons in vivo.
