Abstract
The effects of quinidine alone, ropitoin alone, and in combination with mexiletine at the sodium channel level were studied in isolated guinea pig papillary muscles using a sucrose gap technique. The maximum upstroke velocity (Vmax) was used as an indirect index of the magnitude of the sodium current. With quinidine (24 microM) and ropitoin (1 microM) added, trains of stimuli led to an exponential decline of Vmax to a new steady-state level (use-dependent block). The combination of mexiletine and quinidine decreased use-dependent Vmax block and magnitude of the slow component of reactivation induced by quinidine without modifying its time-constant of recovery. When we studied the interaction between mexiletine and ropitoin, we obtained similar results. Therefore, we conclude that mexiletine, quinidine, and ropitoin may bind to the same receptor site in the sodium channel. In addition, these antagonistic effects appeared only at frequencies greater than 0.5 Hz, whereas at very slow frequencies of stimulation we observed a synergistic effect in both interactions studied.
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