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 isolated and expressed in Xenopus oocytes. The currents, gpI_sK, exhibit many of the electrophysiological and pharmacological properties characteristic of gpI_Ks, the slow component of the delayed rectifier potassium conductance in guinea pig cardiac myocytes. Depolarizing commands evoke outward potassium currents that activate slowly, with time constants on the order of seconds. The currents are blocked by the class III antiarrhythmic compound clofilium but not by the sotalol derivative E4031 or low concentrations of lanthanum. Like I_Ks in guinea pig myocytes, gpI_sK is modulated by stimulation of protein kinase A and protein kinase C (PKC). In contrast to rat and mouse I_sK, which are decreased upon stimulation of PKC, myocyte I_K and gpI_sK in oocytes are increased after PKC stimulation. Substitution of an asparagine residue at position 102 by serine (N102S), the residue found in the analogous position of the mouse and rat min K proteins, results in decreased gpI_sK in response to PKC stimulation. These results support the hypothesis that the min K protein underlies the slow component of the delayed rectifier potassium current in ventricular myocytes and account for the species-specific responses to stimulation of PKC.