自发性高血压大鼠左心室肌细胞电生理研究

The Electrophysiological Study of Left Ventricular Myocytes from Spontaneously Hypertensive Rats

目的 研究自发性高血压大鼠 (SHR)左心室肌细胞的电生理特性。方法 以正常血压Wistar大鼠左心室肌细胞作为对照 ,采用玻璃微电极技术记录动作电位 ,应用膜片钳全细胞技术记录膜离子流 ,观察SHR左心室肌细胞动作电位及膜离子流的改变。结果 ①SHR和Wisar大鼠的心脏 /体重比分别为 5 .6 6± 0 .46mg/g(n =2 0 )和 3.7± 0 .2 9mg/g(n =2 8) (P <0 .0 0 1) ,平均细胞膜电容分别为 2 80 .6 8± 6 7.98pF(n =91)和 189.94± 5 6 .5 9pF(n =137) (P <0 .0 5 )。②SHR左心室肌细胞动作电位时程较Wistar大鼠明显延长 [APD50 :2 1.33± 1.5 6ms(n =6 ) ,vs 14.91± 2 .95ms(n =11) ,P <0 .0 0 1;APD90 :16 4.6 7± 4ms ,vs 93.2 7± 10 .5 9ms ,P <0 .0 0 1]。③内向电流 :SHR左心室肌细胞的ICa -L密度与Wistar大鼠间无差异 [6 .93± 1.71pA/pF(n =2 0 ) ,vs 6 .19± 2 .85pA/pF(n =37) ],但前者的慢失活时间常数显著延长 (5 6 .0 1± 13.36ms,vs 43.6 3± 17.89ms,P <0 .0 0 1)。SHR左心室肌细胞的INa密度与Wistar大鼠间无差异 [2 4.6 1± 6 .72 pA/pF(n =16 ) ,vs 2 4.95± 6 .99pA/pF(n =18) ]。④外向电流 :SHR左心室肌细胞IK1内向电流密度显著小于Wistar大鼠 [- 12 0mV时 ,11.3± 2 .2 6 pA/pF(n =17) 。

Objective To study the electrophysiological characteristics of left ventricular myocytes from spontaneously hypertensive rats (SHR).Methods Using microelectrode technique to record action potential and patch-clamp whole-cell recording to record membrane ionic currents,the changes of action potentials and membrane ionic currents of left ventricular myocytes from SHR were observed whereas the normotensive Wistar rats were used as controls.Results ①The heart weight to body weight ratio of SHR and Wistar rats was 5.66±0.46mg/g(n=20) and 3.7±0.29mg/g(n=28)( P <0.001) respectively,the mean cellular capacitance was 280.68±67.89pF(n=91) and 189.94 ±56.59pF (n=137)( P <0.05).These indicated that there were heart hypertrophy and enlargement of left ventricular myocytes in SHR.②The action potential duration of left ventricular myo cytes from SHR was significantly prolonged than that from Wistar rats[APD 50 :21.33±1.56ms (n= 6),vs 14.91±2.95ms(n=11), P <0.001;APD 90 :164.67±4ms,vs 93.27±10.59ms, P <0.001].This suggested that there was repolarization delay of left ventriculat myocytes from SHR.③ Inward currents:The density of I Ca-L of left ventricular myocytes from SHR was similar to that from Wistar rats[6.93±1.71pA/pF(n=20),vs 6.19±2.85pA/pF(n=37)],but the slow inactivation time constant from SHR was significantly prolonged(56.01±13.36ms,vs 43.63±17.89ms, P <0.001).The density of I Na of left ventricular myocytes from SHR was not different from that from Wistar rats [24.61±6.72 pA/pF(n=16),vs 24.95±6.99pA/pF(n=18)].④Outward currents:The inward current density of I K1 of left ventricular myocytes from SHR was significantly smaller than that from Wistar rats[-120mV,11.3±2.26pA/pF(n=17),vs 14.3±3pA/pF(n=22), P <0.05],but there was no difference in outward curent density(0mV,2.36±0.86pA/pF,vs 2.96±1.27pA/pF).The density of I K of left ventricular myocytes from SHR was similar to that from Wistar rats[+90mV, 12.38 ± 5.46 pA/pF(n=20),vs 11.86±3.59pA/pF(n=37)].The density of I to of left ventricular myocytes from SHR was significantly reduced[+70mV,8.21±6.64pA/pF(n=18),vs 19.16± 6.17 pA/pF(n=23), P <0.001],but activation and inactivation time constants were similar.Conclusion The left ventricular myocytes from SHR have action potential prolongation.No change in inward current density(I Ca-L ,I Na )suggests that the channel number increases as cells become enlarged.The density reduction of outward repolarization potassium currents(I K1 ,I to ,especially I to )indicates that there is repolarization disturbance of hypertrophied left ventricular myocytes in SHR and this contributes to the genesis of ventricular arrhythmias.