Protein Kinase C Activates ATP-sensitive Potassium Channels in Rabbit Ventricular Myocytes

Protein Kinase C Activates ATP-sensitive Potassium Channels in Rabbit Ventricular Myocytes

Several signal transduction pathways have been implicated in ischemic preconditioning induced by the activation of ATP-sensitive K<SUP>&#8290;</SUP> (K<SUB>ATP</SUB>) channels. We examined whether protein kinase C (PKC) modulated the activity of K<SUB>ATP</SUB> channels by recording K<SUB>ATP</SUB> channel currents in rabbit ventricular myocytes using patch-clamp technique and found that phorbol 12,13-didecanoate (PDD) enhanced pinacidil-induced K<SUB>ATP</SUB> channel activity in the cell-attached configuration; and this effect was prevented by bisindolylmaleimide (BIM). K<SUB>ATP</SUB> channel activity was not increased by 4α-PDD. In excised inside- out patches, PKC stimulated K<SUB>ATP</SUB> channels in the presence of 1 mM ATP, and this effect was abolished in the presence of BIM. Heat-inactivated PKC had no effect on channel activity. PKC-induced activation of K<SUB>ATP</SUB> channels was reversed by PP2A, and this effect was not detected in the presence of okadaic acid. These results suggest that PKC activates K<SUB>ATP</SUB> channels in rabbit ventricular myocytes.