Electrophysiological actions of BRL 34915 in isolated guinea pig ventricular myocytes

Specimens of diseased human ventricle and of infarcted cardiac tissue obtained from animal models contain admixtures of both well‐polarized and partially depolarized cells which may contribute to the development of cardiac arrhythmias. Recently, it has been suggested that the partially depolarized potentials result from low potassium permeability (PK) since some of the partially depolarized cells can be hyperpolarized by measures which increase Pk including increased external potassium (K+o) and rapid pacing (McCullough et al.: Circulation 66:II–198, 1982; Circulation 70:II–889, 1984). In the present study, we examined the electrophysiological actions of BRL 34915 (Cromakalim), a vasorelaxant agent reported to increase Pk of vascular smooth muscle cells, on the resting potential (RP) and the background K current (IK1) of isolated guinea pig ventricular myocytes by using whole‐cell voltage‐clamping techniques. BRL 34915 (5 μM) significantly hyperpolarized RP at all K+o tested, the extent of hyperpolarization decreasing with increasing K+o. The slope of the relationship between RP and K+o increased in the presence of BRL 34915 from −41.4 to −54.8 mV. BRL 34915 inhibited IK1 by decreasing the inward current at potentials negative to RP and the outward current between RP and ∼−20 mV. Outward current positive to −20 mV was unaffected. Higher concentrations (50–100 μM) of BRL 34915 increased this current. These results suggest that the hyperpolarization induced by low concentrations of BRL 34915 resulted from an increase in selectively of the membrane for potassium. Higher concentrations may increase an outward potassium current. Potential therapeutic applications of cardiac selective potassium channel activators are discussed.