摘要
To study the difference in membrane ionic currents between hypertrophied and normal myocytes and to explore the electrical remodeling of hypertrophied myocytes Methods Membrane ionic channels were studied in enzymatically dispersed spontaneously hypertensive rats (SHRs) left ventricular myocytes using the whole cell configuration of patch clamp technique, with normal Wistar rats ventricular myocytes as controls We observed depolarizing currents (sodium current, I Na ; L type calcium current, L I Ca ) and repolarizing currents (inward rectifier potassium current, I K1 ; delayed rectifier potassium current, I K; transient outward potassium current, I to ) and compared the differences between normal and hypertrophied myocytes Results The heart to body weight ratio of Wistar rats and SHRs was 3 70±0 29?mg/g and 5 66±0 46?mg/g, respectively ( P <0 001), and the mean cell membrane capacitances were 189 94±56 59?pF and 280 68±67 98?pF, respectively ( P <0 05) These differences suggest that SHRs have heart hypertrophy and hypertrophied myocytes The amplitude of L I ca of SHRs (1944±466 8?pA) was significantly greater than that of Wistar rats (1136±383 3?pA) ( P <0 001), and the current density was 6 93±1 71?pA/pF and 6 19±2 85?pA/pF respectively when normalized to cell capacitance, and the slow inactivation time constant of SHRs was significantly prolonged (56 01±13 36?ms vs 43 63±17 89?ms, P <0 001) The amplitude of I Na of SHRs (6132 5±1162 9?pA) was significantly greater than that of Wistar rats (3613 9±794 44?pA) ( P <0 001), but there was no difference when normalized to cell capacitance (24 61±6 72?pA/pF vs 24 95±6 99?pA/pF) Channel activation and inactivation time constants were also the same The amplitude of I K of SHRs (3461 5±1967 10?pA) was greater than that of Wistar rats (2302 4±893 72?pA) ( P <0 05), but there was no difference when normalized to cell capacitance (12 38±5 46 ?pA/pF vs 11 86±3 59?pA/pF) The inward portion of I K1 of SHRs was significantly lower than that of Wistar rats (11 3±2 26?pA/pF vs 14 3±3 00?pA/pF, P <0 05), but there was no difference in the outward portion (2 360±0 86?pA/pF vs 2 957±1 27? pA/pF) The current density of I to of SHRs (8 21±6 64?pA/pF) was significantly lower than that of Wistar rats (19 16±6 17?pA/pF) ( P <0 001), but channel kinetics were similar, suggesting that the reduction of I to may result from the decrease in channel number Conclusions Membrane ionic current changes of hypertrophied left ventricular myocytes in SHRs include: 1 there was an increase of L I ca , I Na and I k, but the current density was similar to that in normal myocytes, indicating that channel numbers increase as the myocytes become hypertrophied; 2 I to was small in hypertrophied ventricular myocytes and its current density was even smaller, indicating that channel numbers decrease as the myocytes enlarge The former is recognized as a physiologically compensatory change which does not lead to electrophysiological disturbance; the latter is viewed as pathological change, where the reduction of I to may lead to a repolarizing delay in myocytes, prolongation of the action potential and the occurrence of arrhythmias because of repolarizing heterogeneity Therefore, the reduction of I to in hypertrophied myocytes should be recognized as a significant or substantial change of electrical remodeling
To study the difference in membrane ionic currents between hypertrophied and normal myocytes and to explore the electrical remodeling of hypertrophied myocytes Methods Membrane ionic channels were studied in enzymatically dispersed spontaneously hypertensive rats (SHRs) left ventricular myocytes using the whole cell configuration of patch clamp technique, with normal Wistar rats ventricular myocytes as controls We observed depolarizing currents (sodium current, I Na ; L type calcium current, L I Ca ) and repolarizing currents (inward rectifier potassium current, I K1 ; delayed rectifier potassium current, I K; transient outward potassium current, I to ) and compared the differences between normal and hypertrophied myocytes Results The heart to body weight ratio of Wistar rats and SHRs was 3 70±0 29?mg/g and 5 66±0 46?mg/g, respectively ( P <0 001), and the mean cell membrane capacitances were 189 94±56 59?pF and 280 68±67 98?pF, respectively ( P <0 05) These differences suggest that SHRs have heart hypertrophy and hypertrophied myocytes The amplitude of L I ca of SHRs (1944±466 8?pA) was significantly greater than that of Wistar rats (1136±383 3?pA) ( P <0 001), and the current density was 6 93±1 71?pA/pF and 6 19±2 85?pA/pF respectively when normalized to cell capacitance, and the slow inactivation time constant of SHRs was significantly prolonged (56 01±13 36?ms vs 43 63±17 89?ms, P <0 001) The amplitude of I Na of SHRs (6132 5±1162 9?pA) was significantly greater than that of Wistar rats (3613 9±794 44?pA) ( P <0 001), but there was no difference when normalized to cell capacitance (24 61±6 72?pA/pF vs 24 95±6 99?pA/pF) Channel activation and inactivation time constants were also the same The amplitude of I K of SHRs (3461 5±1967 10?pA) was greater than that of Wistar rats (2302 4±893 72?pA) ( P <0 05), but there was no difference when normalized to cell capacitance (12 38±5 46 ?pA/pF vs 11 86±3 59?pA/pF) The inward portion of I K1 of SHRs was significantly lower than that of Wistar rats (11 3±2 26?pA/pF vs 14 3±3 00?pA/pF, P <0 05), but there was no difference in the outward portion (2 360±0 86?pA/pF vs 2 957±1 27? pA/pF) The current density of I to of SHRs (8 21±6 64?pA/pF) was significantly lower than that of Wistar rats (19 16±6 17?pA/pF) ( P <0 001), but channel kinetics were similar, suggesting that the reduction of I to may result from the decrease in channel number Conclusions Membrane ionic current changes of hypertrophied left ventricular myocytes in SHRs include: 1 there was an increase of L I ca , I Na and I k, but the current density was similar to that in normal myocytes, indicating that channel numbers increase as the myocytes become hypertrophied; 2 I to was small in hypertrophied ventricular myocytes and its current density was even smaller, indicating that channel numbers decrease as the myocytes enlarge The former is recognized as a physiologically compensatory change which does not lead to electrophysiological disturbance; the latter is viewed as pathological change, where the reduction of I to may lead to a repolarizing delay in myocytes, prolongation of the action potential and the occurrence of arrhythmias because of repolarizing heterogeneity Therefore, the reduction of I to in hypertrophied myocytes should be recognized as a significant or substantial change of electrical remodeling
