利多卡因对兔心室肌细胞动作电位的影响及对快钠电流的阻滞作用

摘要

目的：探讨利多卡因对心室肌细胞动作电位(AP)的影响以及对快钠电流(INa-T )的张力性阻滞和使用依赖性阻滞作用。方法急性分离新西兰大白兔心脏,并予消化酶消化获得单个心室肌细胞,采用微电极技术检测 AP 相关参数：最大舒张期电位、零相最大上升速率(Vmax)、AP 振幅,以及复极化20%、50%和90%时的 AP 时程(APD20、APD50、APD90)。采用全细胞膜片钳技术检测兔心室肌细胞的 I Na-T。用100μmol/ L 利多卡因溶液灌流干预,观察各参数的变化。结果100μmol/ L 利多卡因灌流后,兔心室肌细胞最大舒张电位无明显变化[(-81±7) mV 比(-80±6)mV,P =0.102], AP 振幅显著降低[(100±12) mV 比(127±9) mV,P =0.002],Vmax 明显减慢[(328±41) V/ s 比(422±45) V/ s, P =0.004],APD90显著缩短[(66±8) ms 比(85±10) ms,P =0.021],峰值钠电流明显降低[(2468±389)pA 比(3223±367)pA,P =0.003]。在5 Hz 频率刺激下,利多卡因灌流前第40个刺激与第1个刺激诱发的电流分别为(3145±323)pA 和(3287±432)pA (P =0.087),灌流后电流分别为(1125±298)pA 和(2365±376)pA(P =0.013)。结论利多卡因降低 AP 振幅,减慢 Vmax,缩短 APD90,对 INa-T不但有张力性阻滞,更有显著的使用依赖性阻滞作用。%Objective To investigate the effects of lidocaine upon the action potential (AP) and its tonic block and use-dependent block of fast sodium current (INa-T ). Methods Hearts of New Zealand white rabbits were acutely separated, digested using enzyme solution, and individual ventricular myocytes were isolated. AP parameters were detected using microelectrode technique including the maximum diastolic potential (MDP), the maximum rate of rise of the action potential upstroke (Vmax), the action potential amplitude (APA) and the action potential duration at 20% , 50% and 90% (APD20 , APD50 and APD90 ) of repolarization. INa-T of rabbit ventricular myocytes was measured using whole cell patch clamp before and after the perfusion of lidocaine. The data obtained were statistically analyzed. Results There was no statistically significant difference in MDP between before and after the perfusion of lidocaine [( - 81 ± 7) mV vs. ( -80 ±6) mV, P =0. 102]. After the perfusion of lidocaine, APA was significantly decreased [(100 ±12) mV vs. (127 ±9) mV, P =0. 002)], Vmax significantly slowed down [ (328 ±41)V/ s vs. (422 ±45)V/ s, P =0. 004], APD90 significantly shortened [(66 ± 8) ms vs. (85 ± 10) ms, P = 0. 021], INa-T significantly decreased [ (2 468 ±389) pA vs. (3 223 ±367) pA, P =0. 003]. Under the stimulation at 5 Hz, there was no statistically significant difference in INa-T between the 40th pulse and the 1st pulse [(3 145 ± 323) pA vs. (3 287 ±432) pA, P =0. 087] before the perfusion of lidocaine; while after the perfusion, the INa-T of the 40th pulse was significantly decreased compared with that of the 1st pulse [(1 125 ± 298) pA vs. (2 365 ± 376) pA, P =0. 013]. Conclusions Lidocaine can reduce the action potential amplitude, slow down the Vmax and shorten APD90. Lidocaine has not only significant tonic block, but marked use-dependent block of INa-T.