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腺苷抗豚鼠室性心律失常的电生理研究

赵正航, 减伟进, 于晓江, 减益民

西安交通大学医学院药理教研室，西安710061；第四军医大学基础部生理教研室，西安710032

摘要

实验用全细胞膜片钳技术在单个豚鼠心室肌细胞上研究了腺普(Ado)对正常及异丙肾上腺素((ISO)致豚鼠心室肌细胞动作电位、迟后除极(DAD) , Lr型钙电流(ICa.L)和短暂内向电流(( 1)的作用。结果表明:(1) Ad。在2。一100 umol/ L时对豚鼠心室肌细胞动作电位和Ica.L无明显直接作用，但却可明显降低Is。所致的动作电位时程APD)延长和Ica.L峰值增大，ISO (10 nmol/ L)使细胞AP DS。从340士21 ms延长到486士28 ms(P< 0.01)，AP D9o从361士17 m、延长至501士29 ms(P<0.01);Ica.L峰值从一6. 53士1.4 pA/pF增大到一18.28士2.4 pA/ pF(P<0. 01)，电流电压曲线明显左移和下移;Ado (50 It mol/ L)使AP DS。和AP Dg。降至403士19 ms和419士26 ms，但并不影响动作电位其它参数，使Ica.L峰值降低至一10.2士1.5 pA/pF (P<0.01)。(2) ISO (30 nmol/ L)可诱发心室肌细胞产生DADS，其发生率为100 %; Ado (50 umol/ L)可完全抑制ISO引发DADS;细胞经一40-+20 m V、时程2s的除极电压，Iso (30 nmol/ L)诱导出入I_(ti)其发生率为100 %; Ado (50 umol/ L)可明显抑制Is。致入1的发生，其发生率降为14.3。研究结果提示，Ado对豚鼠心室肌细胞动作电位和I_(cal)I_(ti)L无明显直接作用，但却可显著降低Is。所致APD的延长、I_(Ca. L)的增加和1_(so)的发生，从而降低细胞内Ca~(2+)的超载，此作用是Ado抑制Iso致DADS的电生理基础。

关键词： 生理学; 电生理研究; 膜片钳技术; 腺苷; 后除极

An electrophysiological study on the arntr verntricular arrhythmic effect of adenosine in the guinea pig

ZHAO Zheng Hang, ZANG Wei-Jin, Yu Xiaojiang, ZANG YiMin

Department of Pharmacology, School of Medicine, Xi'an jiaotong University, Xian 710061； Department of Physiology Fourth Military Medical University, Xi'an 710032

Abstract

Using whole-cell patch clamp technique this study investigated the effects of adenosine(Ado) on action potential，L-type calcium current(1二L)，delayed afterdepolarizations(DADS)，and transient inward current(1) induced by is op rote re nol(ISO) in guinea pig isolated single ventricular myocytes .The results showed:(1)Ado alone had no significant direct effects on action potential and IC,.Lin guinea pig ventricular myocytes at 20一100 umol/ L.However，Ado significant1y attenuated the prolongation of action potential duration(APD) and the increase of the peak amplitude of 1二L induced by SO .ISO(10 nmol/ L) markedly increased APDso and APD9o from 340士21 ms to 486士28 ms and from 361士17 ms to 501士29 ms，respectively(P(0. 01)，and increased the amplitude of 1二L from一6. 53士1.4 pA/ pF to一18. 28士2.4 pA/pF(P(0. 01).The peak potential of current-potential relationship shifted to the left .Ado(50 umol/ L) abbreviated APDso，APD9o to 403士19 ms and 419士26 ms(P(0.01)，and decreased the peak amplitude of 1二Lto一10. 2士1.5pA/ pF(P(0. 01 VS ISO)，but did not change resting membrane potential(RMP)，action potential amplitude(AP A)，and overshoot(08).(2) ISO(30 nmol/ L) reproducibly elicited DADS with 100%incidence of DADS under this condition.Ado (50 umol/ L) completely inhibited ISO from inducing DADS.ISO(30 nmol/ L) elicited l,; with 2-second depolarizing voltageclamp pulses rising to+20 m V from a holding potential of一40 m V，the incidence of 1,; being 100%，and the 1,; was suppressed in the presence of Ado(50 umol/ L) with the incidence of l,; decreased to 14. 3%(P(0. 05).These data indicate that Ado antagonizes the stimulatory effect of ISO，and that the antiarrhythmic mechanism of Ado preventing Isoinduced DADS is due to the inhibition of intracellular Cat+overload through attenuating the prolongation of APD，the enhance of I_(Cal) and I_(ti).

Key words: Physiology;elect rophysiological study;pate卜clamp techniques;Adenosine;delayed afterdepolarization

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引用本文：

赵正航, 减伟进, 于晓江, 减益民. 腺苷抗豚鼠室性心律失常的电生理研究[J]. 生理学报 2003; 55 (1): .

ZHAO Zheng Hang, ZANG Wei-Jin, Yu Xiaojiang, ZANG YiMin. An electrophysiological study on the arntr verntricular arrhythmic effect of adenosine in the guinea pig. Acta Physiol Sin 2003; 55 (1): (in Chinese with English abstract).