Protein kinase C inhibits G protein-gated inwardly rectifying K(+) channels

Abstract

The regulation by Protein Kinase C (PKC) of recombinant G protein-gated Inwardly Rectifying K(+) channels (GIRK channels) expressed in Xenopus oocytes was studied. Phorbol 12-Myristate 13-Acetate (PMA; 1 micro M), an activator of PKC, caused a rapid (up to 40 percent) inhibition of heteromeric GIRK1/4 channels, and only partial recovery occoured after removal of PMA. The current GIRK1/4 inhibition by PMA was prevented by staurosporine (1 micro M), an inhibitor of PKC. Homomeric GIRK4 channels were inhibited similarly by PKC activation. In contrast, homomeric channels of a GIRK1 analogue (GIRK/F137S) were unaffected by PKC activation. These results suggest that the GIRK4 subunit is responsible for PKC-dependent regulation of acetylcholine-sensitive K(+) channel activity in the heart.