THE MIN K-CHANNEL UNDERLIES THE CARDIAC POTASSIUM CURRENT I(KS) AND MEDIATES SPECIES-SPECIFIC RESPONSES TO PROTEIN-KINASE-C

A clone encoding the guinea pig (gp) min K potassium channel was isola ted and expressed in Xenopus oocytes. The currents, gpI(sK), exhibit m any of the electrophysiological and pharmacological properties charact eristic of gpI(Ks), the slow component of the delayed rectifier potass ium conductance in guinea pig cardiac myocytes. Depolarizing commands evoke outward potassium currents that activate slowly, with time const ants on the order of seconds. The currents are blocked by the class II I antiarrhythmic compound clofilium but not by the sotalol derivative E4031 or low concentrations of lanthanum. Like I(Ks) in guinea pig myo cytes, gpI(sK) is modulated by stimulation of protein kinase A and pro tein kinase C (PKC). In contrast to rat and mouse I(sK), which are dec reased upon stimulation of PKC, myocyte I(K) and gpI(sK) in oocytes ar e increased after PKC stimulation. Substitution of an asparagine resid ue at position 102 by serine (N102S), the residue found in the analogo us position of the mouse and rat min K proteins, results in decreased gpI(sK) in response to PKC stimulation. These results support the hypo thesis that the min K protein underlies the slow component of the dela yed rectifier potassium current in ventricular myocytes and account fo r the species-specific responses to stimulation of PKC.