The effects of mexiletine on action potential duration and its restitution in guinea pig ventricular muscles.

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To clarify the mechanism of mexiletine-induced changes in action potential duration (APD), we studied the effects of mexiletine (2μg/ml) on APD at 0mV (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=5.4mM. The percent changes at the three concentrations were 5.0±2.1% at a [K]0 of 2.7mM, 6.0±3.2% at 5.4mM and 1.8±1.2% at 10.0mM 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. SAPD0mV and S-APD90% were more markedly affected when stimulated at a frequency of 1Hz than when stimulated at 0.2 or 0.5Hz. Mexiletine failed to produce any additional APD shortening beyond that produced by the introduction of tetrodotoxin (2.5×10-6M). 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.
International Heart Journal刊行会の論文