Activators of sodium, calcium and potassium channels modulate the cardiac effects of quinidine in vitro.

Quinidine (25.5 mumol/l) reduced the beating frequency of isolated right guinea-pig atria, caused a negative inotropic effect in papillary muscles and slightly raised the contractile force of left atria. The functional refractory period of both tissues was prolonged. A 20% increase of the extracellular sodium concentration did not reverse the effects of quinidine. The Na-channel activator BDF 9148 (1 mumol/l) and the Ca-channel agonist Bay-K-8644 (0.5 mumol/l) further increased the contractile force and caused an additional prolongation of the functional refractory period in quinidine-pretreated atria. Only Bay-K-8644 was able to reverse the negative inotropic effect of quinidine in papillary muscles. The influence of Bay-K-8644 on the contractile force in quinidine-pretreated muscles was not attenuated by lemacalim (3 mumol/l), an activator of ATP-dependent potassium channels, but the duration of the functional refractory period was significantly reduced. These results suggest that a combination of a calcium channel activator and a potassium channel opener might be able to improve the treatment of quinidine intoxications.