IONIC BASES FOR ELECTROPHYSIOLOGICAL DISTINCTIONS AMONG EPICARDIAL, MID-MYOCARDIAL, AND ENDOCARDIAL MYOCYTES FROM THE FREE WALL OF THE CANINE LEFT-VENTRICLE
IONIC BASES FOR ELECTROPHYSIOLOGICAL DISTINCTIONS AMONG EPICARDIAL, MID-MYOCARDIAL, AND ENDOCARDIAL MYOCYTES FROM THE FREE WALL OF THE CANINE LEFT-VENTRICLE
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DOI：
10.1161/01.res.72.3.671
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发表时间：
1993-03-01
影响因子：
20.1
通讯作者：
ANTZELEVITCH, C
中科院分区：
文献类型：
--
作者：
LIU, DW;GINTANT, GA;ANTZELEVITCH, C
我们实验室最近涉及合体细胞准备的研究描绘了心外膜、心内膜和犬心室心外膜下至心肌中层(M区)的独特细胞群之间的电生理差异。在本研究中，我们采用标准微电极、单微电极开关电压钳和全细胞膜片钳技术，检测了酶促分离的犬左室壁离散层心肌细胞的跨膜动作电位、稳态电流-电压关系和4-氨基吡啶敏感的瞬时外向电流(I(To1))。从心外膜、M区和心内膜分离的心肌细胞的动作电位特征与以前从室壁各自区域分离的合胞标本中观察到的非常相似。来自心外膜和M区的心肌细胞有明显的棘突和圆顶，而来自心内膜的心肌细胞没有明显的棘突和圆顶。在分离自M区的细胞中，动作电位时程-频率关系更为显著。从心外膜、M区和心内膜起源的细胞记录到的电流-电压关系均呈N形，具有显著的负斜率-电导区。外膜、M区和心内膜细胞的内向整流钾电流I(K1)分别为392+/-86、289+/-65和348+/-115 pA。当I(K1)被定义为在存在和不存在细胞外K+的情况下(6 Mm)测量的稳态差值电流时，得到类似的水平。心外膜和M区心肌细胞的I(To1)显著大于心内膜心肌细胞。在+70 mV(保持电位，-80 mV)的测试电压下，心外膜、M区和心内膜细胞的I(To1)幅度分别为4203+/-2,370，3,638+/-1,135和714+/-286 pA。在三种细胞类型中，i(To1)失活的电压依赖性没有显著差异。与心外膜或心内膜细胞相比，M区细胞I(To1)重新激活的时间进程较慢。我们的数据表明，犬跨室壁细胞的电生理存在显著的异质性，瞬时外向电流强度的差异对这种异质性起重要作用，但不是唯一的。这些发现将促进我们对基本心脏功能和心电图J波、T波、U波和长QT间期的离子基础的理解，并促进我们对导致心律失常发生的一些复杂因素的理解。
Recent studies from our laboratory involving syncytial preparations have delineated electrophysiological distinctions between epicardium, endocardium, and a unique population of cells in the deep subepicardial to midmyocardial layers (M region) of the canine ventricle. In the present study, we used standard microelectrode, single microelectrode switch voltage-clamp, and whole-cell patch-clamp techniques to examine transmembrane action potentials, steady-state current-voltage relations, and the 4-aminopyridine-sensitive transient outward current (I(to1)) in myocytes enzymatically dissociated from discrete layers of the free wall of the canine left ventricle. Action potential characteristics of myocytes isolated from the epicardium, M region, and endocardium were very similar to those previously observed in syncytial preparations isolated from the respective regions of the ventricular wall. A prominent spike and dome was apparent in myocytes from epicardium and the M region but not in myocytes from endocardium. Action potential duration-rate relations were considerably more pronounced in cells isolated from the M region. Current-voltage relations recorded from cells of epicardial, M region, and endocardial origin all displayed an N-shaped configuration with a prominent negative slope-conductance region. The magnitude of the inward rectifier K+ current (I(K1)) was 392+/-86, 289+/-65, and 348+/-115 pA in epicardial, M region, and endocardial myocytes, respectively, when defined as steady-state current blocked by 10 mM Cs+. Similar levels were obtained when I(K1) was defined as the steady-state difference current measured in the presence (6 mM) and absence of extracellular K+.I(to1) was significantly greater in epicardial and M region myocytes than in endocardial myocytes. At a test potential of +70 mV (holding potential, -80 mV), I(to1) amplitude was 4,203+/-2,370, 3,638+/-1,135, and 714+/-286 pA in epicardial, M region, and endocardial cells, respectively. No significant differences were observed in the voltage dependence of inactivation of I(to1) in the three cell types. The time course of reactivation of I(to1) was slower in cells from the M region compared with either epicardial or endocardial cells. Our data suggest that prominent heterogeneity exists in the electrophysiology of cells spanning the canine ventricular wall and that differences in the intensity of the transient outward current contribute importantly, but not exclusively, to this heterogeneity. These findings should advance our understanding of basic heart function and the ionic bases for the electrocardiographic J wave, T wave, U wave, and long QT intervals as well as improve our understanding of some of the complex factors contributing, to the development of cardiae arrhythmias.