| pubmed-article:2441073 | pubmed:abstractText | The inhibitory effect of disopyramide, quinidine, mexiletine, lidocaine, tocainide and aprindine on the maximum upstroke velocity (Vmax) of action potential was examined in isolated guinea-pig cardiac muscles in terms of their sodium channel block during activated and/or inactivated state. In right ventricular papillary muscles, a conditioning clamp pulse was applied from the resting potential to 0 mV level using the single sucrose-gap voltage clamp technique, and Vmax of test action potential elicited 100 ms after termination of the clamp pulse was measured as an index of sodium channel availability. Such clamp pulses caused various Vmax decreases in the presence of the six drugs. The decrease in Vmax by 10 ms clamp pulse was defined as the activated channel block (ACB), and the decrease in Vmax as the clamp pulse duration was prolonged from 10 to 500 ms was defined as the inactivated channel block (ICB). The ratio of ICB to ACB was less than 1.0 (0.36-0.51) for disopyramide and quinidine, and much greater than 1.0 (2.61-11.23) for mexiletine, lidocaine, tocainide and aprindine. From these findings it was suggested that the former group of drugs may block the sodium channel mainly during the upstroke phase of action potential, while the latter do so mainly during the plateau phase. This assumption was confirmed by experiments comparing the potency of Vmax inhibition in atrial and ventricular muscles isolated from the same guinea-pig heart. | lld:pubmed |
