CHARACTERISTICS OF THE DELAYED RECTIFIER CURRENT (I-KR AND I-KS) IN CANINE VENTRICULAR EPICARDIAL, MIDMYOCARDIAL, AND ENDOCARDIAL MYOCYTES - A WEAKER I-KS CONTRIBUTES TO THE LONGER ACTION-POTENTIAL OF THE M-CELL
CHARACTERISTICS OF THE DELAYED RECTIFIER CURRENT (I-KR AND I-KS) IN CANINE VENTRICULAR EPICARDIAL, MIDMYOCARDIAL, AND ENDOCARDIAL MYOCYTES - A WEAKER I-KS CONTRIBUTES TO THE LONGER ACTION-POTENTIAL OF THE M-CELL
复制标题
DOI：
10.1161/01.res.76.3.351
复制
发表时间：
1995-03-01
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;ANTZELEVITCH, C
最近的研究已经描述了犬、猫、大鼠、豚鼠和人类心脏心室肌电生理学和药理学的区域差异。本研究采用标准微电极和全细胞膜片钳技术，观察了犬左心室心外膜、M区（心外膜下至心肌中层）和内膜细胞的动作电位和延迟整流钾电流（I-K）的特性。从M.动作电位时程（APD）在慢速率下明显延长。在基本周期长度为4 s时，M区、心外膜和内膜细胞在90%复极化时测得的APD分别为358+/-16（平均值+/-SEM）、262+/-12和287+/-11 ms。稳态APD率的关系是陡峭的细胞从M区。在完全台氏液中，与心外膜或内膜分离的心肌细胞相比，M区心肌细胞的I-K较小。在无Na+、K+和Ca 2+的浴溶液中进行I-K的进一步表征，以将延迟整流器的缓慢活化组分（I-Ks）与快速活化组分（I-Kr）分离。M细胞的I-Ks明显小于心外膜和内膜细胞。复极化至-20 mV时，心外膜细胞的I-Ks尾电流密度为1.99+/-0.30 pA/pF（平均值+/-SEM），内皮细胞为1.83+/-0.18 pA/pF，M细胞为0.92+/-0.14 pA/pF。I-Ks的激活和失活的电压依赖性和时间过程在三种细胞类型中是相似的。用6 mmol/L [K+]（o）Tyrode液加或不加高选择性I-Kr阻断剂E-4031检测I-Kr和I-Ks在三种细胞类型中的相对贡献。E-4031敏感电流的存在下，但不是在细胞外K+的情况下观察到的。这种快速激活的成分显示出与兔和猫心室细胞中所描述的I-Kr相似的特征。I-Kr的失活明显慢于I-Ks。I-Kr（E-4031敏感组分）尾电流密度在三种细胞类型中相似，而I-Ks（E-4031不敏感组分）尾电流密度在M细胞中显著较小。我们的研究结果表明，M细胞独特的3相复极功能部分是由于I-Ks的贡献较小，这种区别也可以解释为什么M细胞是延长心室肌APD的药物的主要靶点。这些发现可能会促进我们对心电图T波、U波和长QT间期的离子基础的理解，以及我们对心律失常发生因素的理解。
Recent studies have described regional differences in the electrophysiology and pharmacology of ventricular myocardium in canine, feline, rat, guinea pig, and human hearts. In this study, we use standard microelectrode and whole-cell patch-clamp techniques to examine the characteristics of the action potential and the delayed rectifier K+ current (I-K) in epicardial, M region (deep subepicardial to midmyocardial), and endocardial cells isolated from the canine left ventricle. Cells from the M. region displayed much longer action potential durations (APDs) at slow rates. At a basic cycle length of 4 s, APD measured at 90% repolarization was 358+/-16 (mean+/-SEM), 262+/-12, and 287+/-11 ms in cells from the M region, epicardium, and endocardium, respectively. Steady state APD-rate relations were steeper in cells from the M region. In complete Tyrode's solution, I-K was smaller in myocytes from the M region when compared with those isolated from the epicardium or endocardium. Further characterization of I-K was conducted in a Na+-, K+-, and Ca2+-free bath solution to isolate the slowly activating component of the delayed rectifier (I-Ks) from the rapidly activating component (I-Kr). I-Ks was significantly smaller in M cells than in epicardial and endocardial cells. With repolarization to -20 mV, I-Ks tail current density was 1.99+/-0.30 pA/pF (mean+/-SEM) in epicar dial cells, 1.83+/-0.18 pA/pF in endocardial cells, and 0.92+/-0.14 pA/pF in M cells. Voltage dependence and time course of activation and deactivation of I-Ks were similar in the three cell types. The relative contribution of I-Kr and I-Ks among the three cell types was examined by using 6 mmol/L [K+](o) Tyrode's solution with and without E-4031, a highly selective blocker of I-Kr. An E-4031-sensitive current was observed in the presence but not in the absence of extracellular K+. This rapidly activating component showed characteristics similar to those of I-Kr as described in rabbit and cat ventricular cells. Deactivation of I-Kr was significantly slower than that of I-Ks. I-Kr (E-4031-sensitive component) tail current density was similar in the three cell types, whereas I-Ks (E-4031-insensitive component) tail current density was significantly smaller in the M cells. Our results suggest that the distinctive phase-3 repolarization features of M cells are due in part to a lesser contribution of I-Ks and that this distinction may also explain why M cells are the main targets for agents that prolong APD in ventricular myocardium. These findings may advance our understanding of the ionic basis for the electrocardiographic T wave, U wave, and long QT intervals as well as our understanding of factors contributing to the development of cardiac arrhythmias.