Effect of class I antiarrhythmic agents on slow Ca2+ channels of myocardial cells

The effects of several class I antiarrhythmic drugs (aprindine, cibenzoline, disopyramide, mexiletine, lidocaine, tocainide and 711389-S) were studied on slow Ca2+ channels of rabbit sinus node cells using a double microelectrode voltage clamp technique. All these drugs decreased the heart rate, the maximum rate of rise (Vmax), the action potential amplitude and the slope of the phase 4 depolarization in spontaneously beating sinus node preparations. The order of inhibitory potency on the heart rate was: aprindine greater than 711389-S greater than cibenzoline greater than or equal to disopyramide greater than mexiletine greater than or equal to lidocaine greater than tocainide. On the current systems, these drugs decreased the slow inward current (Isi) and the time-dependent potassium current (Ik). However, the major effect was a reduction of Isi. These agents also exerted a frequency-dependent block of Isi. Furthermore, comparing the effects of class I antiarrhythmic agents on slow Ca2+ channels, the order of inhibitory effect on Vmax of sinus node cells was: aprindine greater than 711389-S greater than cibenzoline greater than or equal to disopyramide greater than mexiletine greater than lidocaine greater than tocainide. These electrophysiological observations suggest that class I antiarrhythmic drugs have a depressant effect on slow Ca2+ channels as well as fast Na+ channels of myocardial cells, and that so-called "slow" kinetic drugs may depress slow Ca2+ channels more strongly than "fast" kinetic drugs.