Electrophysiological actions of mexiletine on rabbit sinoatrial node cells

The effects of mexiletine (1-100 microM) were examined on membrane potential and current of rabbit sinoatrial node cells by means of conventional microelectrode and double microelectrode voltage clamp techniques. Mexiletine decreased, in a dose-dependent manner, the maximum rate of depolarization of the action potential and the action potential amplitude, and increased the spontaneous cycle length. The slope of the diastolic depolarization (phase 4) was also reduced. In the voltage clamp experiment, mexiletine (40-100 microM) reduced the slow inward current (Isi), the potassium outward current (IK) and the hyperpolarization-activated current (Ih). The kinetic variable of IK was not altered by the drug. These results suggest that mexiletine does not have a specific effect on a single-current system, but that relatively high concentrations of mexiletine exert an inhibitory effect on the electrical activity of the sinoatrial node cells.