自发性高血压大鼠左心室肌细胞动作电位延长的离子机制

The Ionic Mechanism of Prolongation of Action Potential in Hypertrophied Left Ventricular Myocytes from Spontaneously Hypertensive Rats

目的：研究自发性高血压大鼠（ＳＨＲ）左心室肌细胞动作电位时程延长的膜离子流基础。方法：应用酶解方法分离获得正常血压Ｗｉｓｔａｒ大鼠和ＳＨＲ的左心室肌细胞，采用玻璃微电极技术记录动作电位，膜片钳全细胞记录膜离子流，对比正常心室肌细胞和肥大心室肌细胞间动作电位及膜离子流差别。结果：（１）ＳＨＲ和Ｗｉｓｔａｒ大鼠的心脏／体重比分别为５．６６±０．４６ ｍｇ／ｇ和 ３．７±０．２９ ｍｇ／ｇ（Ｐ＜０．００１），细胞平均膜电容分别为 ２８０．６８±６７．９８ ｐＦ和 １８９．９４±５６．５９ ｐＦ（Ｐ＜０．０５）。提示ＳＨＲ心脏肥厚、心肌细胞增大；（２）ＳＨＲ动作电位ＡＰＤ５０和 ＡＰＤ９０较Ｗｉｓｔａｒ大鼠明显延长（２１．３３±１． ５６ ｍｓ ｖｓ １４． ９１±２．９５ ｍｓ，Ｐ＜０．００１； １６４． ６±７４ ｍｓ ｖｓ ９３．２７±１０． ５９ ｍｓ，Ｐ＜０．００１），说明ＳＨＲ心室肌细胞存在复极延迟；（３）ＳＨＲ的平均 Ｉ_（Ｃａ－Ｌ）幅值显著大于Ｗｉｓｔａｒ大鼠，分别为 １９４４±４６６． ８ ｐＡ和１１３６±３３．３ ｐＡ（Ｐ＜０．００１），电流密度二者间无差异（６． ９３２±１．７１ ｐＡ／ＰＦ ｖｓ ６．１９±２．８５ ｐＡ／?

Objective: To study the membrane ionic basis of action potential prolongation of hypertrophied left ventricular myocytes in spontaneously hypertensive rats (SHR ). Methods: The single left ventricular myocytes of SHR and normotensive Wistar rats were obtained enzymatically. The action potential was recorded using conventional microelec- trode technique and membrane ionic currents were recorded using patch-clamp whole cell recording technique. The action potential and membrane ionic currents of normal and hypertrophied left ventricular myocytes were compared. Results: (1)The heart weight to body weight ratio of SHR and Wistar rats was 5. 66±0. 46 mg/g and 3. 7± 0. 29 mg/g, respectively(p<0. 001), and the mean cell membrane capacitance, 280. 68± 67. 98 pF and 189. 94± 56. 59 pF, respectively (P< 0. 05 ), suggesting that SHR had heart hypertrophy and hypertrophied ventricular myocytes; (2) The APD_(50) and APD_(90) of action potential in SHR was significantly prolonged compared with Wistar rats (21. 33±1. 56 ms vs 14. 91 ± 2. 95 ms, P<0. 001 ± 164. 6± 7. 4 ms vs 93. 27± 10. 59 ms, P<0. 001 ), indicating that the left ventricular myocytes in SHR had delayed repolarization ; (3)The amplitude of I_(ca-L) of SHR (1944 ± 466. 8 pA) at + 10 mV was significantly greater than that of Wistar rats (1136 ± 383. 3 pA) (P< 0. 001 ), the current density of I_(ca-L) between them was not significant (6. 93 ± 1. 71 pA/pF vs 6. 19± 2. 85 pA/pF), but the slow inactivation time constant of SHR was significantly prolonged (56. 01 ± 13. 36 ms vs 43. 63± 17. 89 ms, P<0. 001 ) ; (4)The inward current density of I_(K1) in SHR at - 120 mV was significantly lower than that in Wistar rats (11. 3± ± 2. 26 pA/pF vs 14. 33 pA/ pF, P<0. 05), but there was no difference in outward current density at 0 mV(2. 36± 0. 86 pA/pF vs 2. 96± 1. 27 pA/ pF) ; (5)There was no difference in current density of I_k at + 90 mV between SHR and Wistar rats(12. 38± 5. 46 pA/pF vs 11. 86± 3. 59 pA/pF) ; (6)The current density of ito in SHR at + 70 mV was significantly lower than that in Wistar rats (8. 21 ± 6. 64 pA/pF vs 19. 16± 6. 17 pA/pF, P<0. 001 ). but the activation and inactivation time constants were similar. This indicated that the reduced ito may result from the decrease of channel numbers. Conclusion: The action potential prolongation of hypertro- phied left ventricular myocytes in SHR may result from the reduction of outward repolarizing potassium currents (I_(to), I_(K1) ) and the prolongation of slow inactivation time constant of I_(ca-L).