Matsuo S, Kishida H, Munakata K, Atarashi H
Jpn Heart J. 1985 Mar;26(2):271-87. doi: 10.1536/ihj.26.271.
To clarify the mechanism of mexiletine-induced changes in action potential duration (APD), we studied the effects of mexiletine (2 micrograms/ml) on APD at 0 mV (APD0mV) and 90% (APD90%) repolarization and on restitution of premature responses in guinea pig ventricular muscle at three extracellular potassium concentrations [( K]0) and three stimulation rates using standard microelectrode techniques. The rates at which APD0mV and APD90% were shortened by mexiletine (S-APD0mV and S-APD90%) expressed as percent change from control were most pronounced at [K]0 = 5.4 mM. The percent changes at the three concentrations were 5.0 +/- 2.1% at a [K]0 of 2.7 mM, 6.0 +/- 3.2% at 5.4 mM and 1.8 +/- 1.2% at 10.0 mM for S-APD0mV and 2.0 +/- 1.9%, 4.7 +/- 2.0% and 1.3 +/- 1.5% for S-APD90% at the same concentrations, respectively. S-APD0mV and S-APD90% were more markedly affected when stimulated at a frequency of 1 Hz than when stimulated at 0.2 or 0.5 Hz. Mexiletine failed to produce any additional APD shortening beyond that produced by the introduction of tetrodotoxin (2.5 X 10(-6) M). Mexiletine and tetrodotoxin did not influence APD restitution that fitted a single exponential curve. We conclude that the shortening of APD by mexiletine results from inhibition of a tetrodotoxin-sensitive sodium current.
为了阐明美西律引起动作电位时程（APD）变化的机制，我们采用标准微电极技术，研究了美西律（2微克/毫升）在三种细胞外钾浓度[（K）0]和三种刺激频率下对豚鼠心室肌0 mV（APD0mV）和90%复极化时的APD（APD90%）以及早搏反应恢复的影响。美西律缩短APD0mV和APD90%的速率（S-APD0mV和S-APD90%）以相对于对照的百分比变化表示，在[K]0 = 5.4 mM时最为明显。在三种浓度下，S-APD0mV在[K]0为2.7 mM时的百分比变化为5.0±2.1%，在5.4 mM时为6.0±3.2%，在10.0 mM时为1.8±1.2%；S-APD90%在相同浓度下分别为2.0±1.9%、4.7±2.0%和1.3±1.5%。当以1 Hz频率刺激时，S-APD0mV和S-APD90%比以0.2或0.5 Hz频率刺激时受到的影响更明显。美西律除了通过引入河豚毒素（2.5×10（-6）M）所产生的APD缩短外，未能产生任何额外的APD缩短。美西律和河豚毒素不影响符合单指数曲线的APD恢复。我们得出结论，美西律引起的APD缩短是由于对河豚毒素敏感的钠电流受到抑制。
