Sicouri S, Quist M, Antzelevitch C
Masonic Medical Research Laboratory, Utica, New York 13501, USA.
J Cardiovasc Electrophysiol. 1996 Jun;7(6):503-11. doi: 10.1111/j.1540-8167.1996.tb00557.x.
Recent studies have described the presence of M cells in the deep layers of the canine and human ventricle displaying electrophysiologic and pharmacologic features different from those of epicardial (EPI) and endocardial (ENDO) cells. The M cell is distinguished electrophysiologically by the ability of its action potential to prolong disproportionately to that of other myocardial cells with slowing of the stimulation rate and pharmacologically by its unique sensitivity to Class III antiarrhythmic agents. The present study was designed to test the hypothesis that similar cells are present in the guinea pig ventricle.
We used a dermatome to obtain-thin strips of left ventricular free wall from the hearts of guinea pigs (8 to 14 weeks old) and standard microelectrode techniques to record transmembrane activity. Action potential duration measured at 90% repolarization (APD90) was significantly longer in mid-myocardial (MID) cells than in surface EPI or ENDO cells at all basic cycle lengths (BCLs) tested. At a BCL of 300 msec, APD90 was 102 +/- 21,136 +/- 9, and 95 +/- 15 msec in EPI, MID, and ENDO cells (mean +/- SD; n = 12). At a BCL of 5000 msec, APD90 was 133 +/- 14, 185 +/- 24, and 135 +/- 13 msec in EPI, MID, and ENDO cells ([K+]o = 4 mM). Thus, APD-rate relations were more pronounced in the MID cells. MID cells were also more sensitive to agents with Class III actions (e.g., d,I-sotalol: 10 to 100 microM), exhibiting a greater APD prolongation than EPI or ENDO. d,I-Sotalol also induced early afterdepolarizations in MID cells but not in EPI or ENDO cells. The rate of rise of the action potential upstroke (Vmax) was significantly greater in MID cells: 129 +/- 13, 240 +/- 42, and 192 +/- 28 V/sec in EPI, MID, and ENDO cells (n = 10 to 18).
Our results demonstrate the existence of important transmural electrical heterogeneity in guinea pig ventricular myocardium. The study provides data in support of the existence of M cells in the mid-myocardial layers of the guinea pig ventricle exhibiting longer APDs and a greater sensitivity to agents with Class III antiarrhythmic action.
最近的研究表明，犬类和人类心室深层存在M细胞，其电生理和药理特性与心外膜（EPI）和心内膜（ENDO）细胞不同。M细胞在电生理上的特征是，随着刺激频率减慢，其动作电位的延长与其他心肌细胞不成比例，在药理上则表现为对III类抗心律失常药物具有独特的敏感性。本研究旨在验证豚鼠心室中是否存在类似细胞的假说。
我们使用皮肤刀从豚鼠（8至14周龄）心脏获取左心室游离壁的薄条带，并采用标准微电极技术记录跨膜活动。在所有测试的基本周期长度（BCL）下，中层心肌（MID）细胞在90%复极化时测量的动作电位持续时间（APD90）显著长于表面EPI或ENDO细胞。在300毫秒的BCL时，EPI、MID和ENDO细胞的APD90分别为102±21、136±9和95±15毫秒（平均值±标准差；n = 12）。在5000毫秒的BCL时，EPI、MID和ENDO细胞的APD90分别为133±14、185±24和135±13毫秒（[K⁺]o = 4 mM）。因此，APD-频率关系在MID细胞中更为明显。MID细胞对具有III类作用的药物（如d，l-索他洛尔：10至100微摩尔）也更敏感，与EPI或ENDO相比，APD延长更明显。d，l-索他洛尔还在MID细胞中诱导早期后去极化，但在EPI或ENDO细胞中未诱导。MID细胞动作电位上升速率（Vmax）显著更高：EPI、MID和ENDO细胞的Vmax分别为129±13、240±42和192±28伏/秒（n = 10至18）。
我们的结果表明豚鼠心室心肌存在重要的跨壁电不均一性。该研究提供的数据支持豚鼠心室中层心肌存在M细胞，这些细胞表现出更长的APD以及对III类抗心律失常作用药物更高的敏感性。
