Using patch clamp whole cell recording techiques, we examined the effects ofIQ_23, a benzyl-isoquinoline derivative with antiarrhythmic activities, on the action potential (AP) andpotassium currents in single guinea p...Using patch clamp whole cell recording techiques, we examined the effects ofIQ_23, a benzyl-isoquinoline derivative with antiarrhythmic activities, on the action potential (AP) andpotassium currents in single guinea pig ventricular myocytes. The results showed that IQ_23 at 10, 30and 100 μmol ·L_-1 slowed the repolarization in AP dose-dependently. The APD_90 were prolonged by15%, 28% and 31% respectively. This effect did not depend on the extracellular Ca^2+. In voltageclamp mode, IQ_23 effectively blocked both the components of the delayed rectifier potassium current(I_k), i.e., I_ks and I_kr. At concentrations of 30 and 100 μmol· L^-1, IQ_23 suppressed I_ks by 21% and 26%and suppressed I_kr by 67% and 86% respectively. But even at 100 μmol·L^-1, IQ_23 had little effect onthe inward rectifier potassium current (I_k1). It is concluded: 1. IQ_23 can dose-dependently prolongAPD in the ventriculas myocytes of guinea pig, the effect does not depend on the extracellular Ca^2+; 2.IQ_23 blocks both I_ks and Ikr in the ventricular myocytes without obvious specificities between them.展开更多
Using patch clamp whole cell recording techiques, we examined the effects ofIQ<sub>2</sub>3, a benzyl-isoquinoline derivative with antiarrhythmic activities, on the action potential （AP） andpotassium cur...Using patch clamp whole cell recording techiques, we examined the effects ofIQ<sub>2</sub>3, a benzyl-isoquinoline derivative with antiarrhythmic activities, on the action potential （AP） andpotassium currents in single guinea pig ventricular myocytes. The results showed that IQ<sub>2</sub>3 at 10, 30and 100 μmol ·L<sub>-</sub>1 slowed the repolarization in AP dose-dependently. The APD<sub>9</sub>0 were prolonged by15%, 28% and 31% respectively. This effect did not depend on the extracellular Ca<sup>2</sup>+. In voltageclamp mode, IQ<sub>2</sub>3 effectively blocked both the components of the delayed rectifier potassium current（I<sub>k</sub>）, i.e., I<sub>k</sub>s and I<sub>k</sub>r. At concentrations of 30 and 100 μmol· L<sup>-</sup>1, IQ<sub>2</sub>3 suppressed I<sub>k</sub>s by 21% and 26%and suppressed I<sub>k</sub>r by 67% and 86% respectively. But even at 100 μmol·L<sup>-</sup>1, IQ<sub>2</sub>3 had little effect onthe inward rectifier potassium current （I<sub>k</sub>1）. It is concluded: 1. IQ<sub>2</sub>3 can dose-dependently prolongAPD in the ventriculas myocytes of guinea pig, the effect does not depend on the extracellular Ca<sup>2</sup>+; 2.IQ<sub>2</sub>3 blocks both I<sub>k</sub>s and Ikr in the ventricular myocytes without obvious specificities between them.展开更多
Aim To determine the effects of glucose on APD, I_(K1) , I_K , I_(Ca-L), ofventricular myocytes in guinea pigs, Methods Whole-cell patch-clamp technique was used to record thechanged action potential ionic current ind...Aim To determine the effects of glucose on APD, I_(K1) , I_K , I_(Ca-L), ofventricular myocytes in guinea pigs, Methods Whole-cell patch-clamp technique was used to record thechanged action potential ionic current induced by glucose of single cell in guinea pig ventricularmyocytes, to compare the action of 0, 10 and 20 mmol·L^(-1) glucoses on trans-membrane ioniccurrent. Results (1) Compared with 10 mmol·L^(-1) glucose concentrations, 0 and 20 mmol·L^(-1)glucose both shortened APD of ventricular myocytes ( P < 0.05). (2) The inward components ofI_(K1) density were maximal when the glucose concentration was at 10 mmol·L^(-1) . Normalized Ⅰ -Ⅴ relationships showed that both 0 and 20 mmol·L^(-1) glucose produced a left-shift of Ⅰ - Ⅴcurve. The reverse potential changed from - 72.4 mV to - 64.6 mV. (3) Compared with 10 mmol·L^(-1),both 0 and 20 mmol·L^(-1) glucose markedly increased the I_(Ca-L) amplitude and density. TheI_(Ca-L) current density was ( - 8.035 +- 0.82) pA/pF ( n = 8) at a test potential of 10 mV when theglucose concentration was 10 mmol·L^(-1) . But its current density decreased to ( - 5.45 +- 0.67)pA/pF and ( - 6.50 +- 0.56) pA/pF when glucose concentrations were 0 and 20 mmol·L^(-1) ,respectively. (4) The current densities of I_K were (18.96+-2.86) pA/pF, (8.66 +-1.87) pA/pF, and(15.32 +- 3.12) pA/pF, at + 70 mV for 0, 10 and 20 mmol·L^(-1) glucoses, respectively. ConclusionGlucose in different concentrations has different effects on APD, I_(K1), I_K, and I_(Ca-L) ofsingle ventricular myocyte in guinea pigs. There are similar actions of 0 and 20 mmol· L^(-1)glucoses on the transmembrane ionic current of ventricular myocytes in guinea pigs.展开更多
Dysregulation of intracellular Ca2+ homeostasis is associated with various pathological conditions and arrhythmogenesis of the heart.The objective of this study was to investigate the effects of an acute increase in i...Dysregulation of intracellular Ca2+ homeostasis is associated with various pathological conditions and arrhythmogenesis of the heart.The objective of this study was to investigate the effects of an acute increase in intracellular Ca2+ concentration ([Ca2+] i) on the electrophysiology of ventricular myocytes by mimicking intracellular Ca 2+ overload.The [Ca2+] i was clamped to either a controlled (65-100 nmol L-1) or increased (1 μmol L-1) level.The transmembrane action potentials and ionic currents were recorded using whole-cell patch clamp techniques.We found that the acute increase in [Ca2+] i shortened the action potential duration,reduced the action potential amplitude,maximum depolarization velocity and resting membrane potential,caused delayed after-depolarizations (DADs),and triggered activity--compared with these parameters in the control.The increased [Ca2+] i augmented late I Na in a time-dependent manner,reduced ICaL and IK1,and increased IKr but not IKs.The results of this study can be used to explain calcium overload-induced ventricular arrhythmias.展开更多
文摘Using patch clamp whole cell recording techiques, we examined the effects ofIQ_23, a benzyl-isoquinoline derivative with antiarrhythmic activities, on the action potential (AP) andpotassium currents in single guinea pig ventricular myocytes. The results showed that IQ_23 at 10, 30and 100 μmol ·L_-1 slowed the repolarization in AP dose-dependently. The APD_90 were prolonged by15%, 28% and 31% respectively. This effect did not depend on the extracellular Ca^2+. In voltageclamp mode, IQ_23 effectively blocked both the components of the delayed rectifier potassium current(I_k), i.e., I_ks and I_kr. At concentrations of 30 and 100 μmol· L^-1, IQ_23 suppressed I_ks by 21% and 26%and suppressed I_kr by 67% and 86% respectively. But even at 100 μmol·L^-1, IQ_23 had little effect onthe inward rectifier potassium current (I_k1). It is concluded: 1. IQ_23 can dose-dependently prolongAPD in the ventriculas myocytes of guinea pig, the effect does not depend on the extracellular Ca^2+; 2.IQ_23 blocks both I_ks and Ikr in the ventricular myocytes without obvious specificities between them.
文摘Using patch clamp whole cell recording techiques, we examined the effects ofIQ<sub>2</sub>3, a benzyl-isoquinoline derivative with antiarrhythmic activities, on the action potential （AP） andpotassium currents in single guinea pig ventricular myocytes. The results showed that IQ<sub>2</sub>3 at 10, 30and 100 μmol ·L<sub>-</sub>1 slowed the repolarization in AP dose-dependently. The APD<sub>9</sub>0 were prolonged by15%, 28% and 31% respectively. This effect did not depend on the extracellular Ca<sup>2</sup>+. In voltageclamp mode, IQ<sub>2</sub>3 effectively blocked both the components of the delayed rectifier potassium current（I<sub>k</sub>）, i.e., I<sub>k</sub>s and I<sub>k</sub>r. At concentrations of 30 and 100 μmol· L<sup>-</sup>1, IQ<sub>2</sub>3 suppressed I<sub>k</sub>s by 21% and 26%and suppressed I<sub>k</sub>r by 67% and 86% respectively. But even at 100 μmol·L<sup>-</sup>1, IQ<sub>2</sub>3 had little effect onthe inward rectifier potassium current （I<sub>k</sub>1）. It is concluded: 1. IQ<sub>2</sub>3 can dose-dependently prolongAPD in the ventriculas myocytes of guinea pig, the effect does not depend on the extracellular Ca<sup>2</sup>+; 2.IQ<sub>2</sub>3 blocks both I<sub>k</sub>s and Ikr in the ventricular myocytes without obvious specificities between them.
文摘Aim To determine the effects of glucose on APD, I_(K1) , I_K , I_(Ca-L), ofventricular myocytes in guinea pigs, Methods Whole-cell patch-clamp technique was used to record thechanged action potential ionic current induced by glucose of single cell in guinea pig ventricularmyocytes, to compare the action of 0, 10 and 20 mmol·L^(-1) glucoses on trans-membrane ioniccurrent. Results (1) Compared with 10 mmol·L^(-1) glucose concentrations, 0 and 20 mmol·L^(-1)glucose both shortened APD of ventricular myocytes ( P < 0.05). (2) The inward components ofI_(K1) density were maximal when the glucose concentration was at 10 mmol·L^(-1) . Normalized Ⅰ -Ⅴ relationships showed that both 0 and 20 mmol·L^(-1) glucose produced a left-shift of Ⅰ - Ⅴcurve. The reverse potential changed from - 72.4 mV to - 64.6 mV. (3) Compared with 10 mmol·L^(-1),both 0 and 20 mmol·L^(-1) glucose markedly increased the I_(Ca-L) amplitude and density. TheI_(Ca-L) current density was ( - 8.035 +- 0.82) pA/pF ( n = 8) at a test potential of 10 mV when theglucose concentration was 10 mmol·L^(-1) . But its current density decreased to ( - 5.45 +- 0.67)pA/pF and ( - 6.50 +- 0.56) pA/pF when glucose concentrations were 0 and 20 mmol·L^(-1) ,respectively. (4) The current densities of I_K were (18.96+-2.86) pA/pF, (8.66 +-1.87) pA/pF, and(15.32 +- 3.12) pA/pF, at + 70 mV for 0, 10 and 20 mmol·L^(-1) glucoses, respectively. ConclusionGlucose in different concentrations has different effects on APD, I_(K1), I_K, and I_(Ca-L) ofsingle ventricular myocyte in guinea pigs. There are similar actions of 0 and 20 mmol· L^(-1)glucoses on the transmembrane ionic current of ventricular myocytes in guinea pigs.
基金supported by the National Natural Science Foundation of China(Grant No. 30870912)Department of Biology,Gilead Sciences,Inc.,USA.
文摘Dysregulation of intracellular Ca2+ homeostasis is associated with various pathological conditions and arrhythmogenesis of the heart.The objective of this study was to investigate the effects of an acute increase in intracellular Ca2+ concentration ([Ca2+] i) on the electrophysiology of ventricular myocytes by mimicking intracellular Ca 2+ overload.The [Ca2+] i was clamped to either a controlled (65-100 nmol L-1) or increased (1 μmol L-1) level.The transmembrane action potentials and ionic currents were recorded using whole-cell patch clamp techniques.We found that the acute increase in [Ca2+] i shortened the action potential duration,reduced the action potential amplitude,maximum depolarization velocity and resting membrane potential,caused delayed after-depolarizations (DADs),and triggered activity--compared with these parameters in the control.The increased [Ca2+] i augmented late I Na in a time-dependent manner,reduced ICaL and IK1,and increased IKr but not IKs.The results of this study can be used to explain calcium overload-induced ventricular arrhythmias.
