Zygmunt A C, Eddlestone G T, Thomas G P, Nesterenko V V, Antzelevitch C
Department of Experimental Cardiology, Masonic Medical Research Laboratory, Utica, New York 13501-1787, USA.
Am J Physiol Heart Circ Physiol. 2001 Aug;281(2):H689-97. doi: 10.1152/ajpheart.2001.281.2.H689.
Action potentials and whole cell sodium current were recorded in canine epicardial, midmyocardial, and endocardial myocytes in normal sodium at 37 degrees C. Tetrodotoxin (TTX) reduced the action potential duration of midmyocardial cells to a greater degree than either epicardial or endocardial cells. Whole cell recordings in potassium-free and very-low-chloride solutions revealed a slowly decaying current that was completely inhibited by 5 microM TTX or replacement of external and internal sodium with the impermeant cation N-methyl-D-glucamine. Late sodium current density at 0 mV was 47% greater in midmyocardial cells and averaged -0.532 +/- 0.058 pA/pF in endocardial, -0.463 +/- 0.068 pA/pF in epicardial, and -0.785 +/- 0.070 pA/pF in midmyocardial cells. Neither the frequency dependence of late sodium current nor its recovery from inactivation exhibited transmural differences. After a 4.5-s pulse to -30 mV, late sodium current recovered with a single time constant of 140 ms. We conclude that a larger late sodium conductance in midmyocardial cells will favor longer action potentials in these cells. More importantly, drugs that slow inactivation of sodium channels will produce a nonuniform response across the ventricular wall that is proarrhythmic.
在37℃正常钠浓度条件下，记录犬心外膜、心肌中层和心内膜心肌细胞的动作电位和全细胞钠电流。河豚毒素（TTX）使心肌中层细胞动作电位时程缩短的程度大于心外膜或心内膜细胞。在无钾和极低氯溶液中的全细胞记录显示，存在一种缓慢衰减的电流，该电流可被5μM TTX或用不透膜阳离子N-甲基-D-葡糖胺替代细胞外和细胞内钠完全抑制。在0 mV时，心肌中层细胞的晚钠电流密度比心内膜细胞大47%，心内膜细胞平均为-0.532±0.058 pA/pF，心外膜细胞为-0.463±0.068 pA/pF，心肌中层细胞为-0.785±0.070 pA/pF。晚钠电流的频率依赖性及其从失活状态的恢复均未表现出跨壁差异。在给予-30 mV的4.5秒脉冲后，晚钠电流以140 ms的单一时间常数恢复。我们得出结论，心肌中层细胞中较大的晚钠电导将有利于这些细胞产生更长的动作电位。更重要的是，减慢钠通道失活的药物将在心室壁上产生不均匀的反应，从而导致心律失常。
