Potentiation of large-conductance calcium-activated potassium (BK(Ca)) channels by a specific isoform of protein kinase C.

The phosphorylation state of large-conductance calcium-activated potassium (BK(Ca)) channels regulates their activity and is dynamically regulated by protein phosphatases and kinases, including protein kinase C (PKC). In this study, we showed that PKC activators up-regulate the activity of the BK(Ca) channel alpha (alpha)-subunit, Slo1, in cell-attached patches of transfected COS7 cells. In an immune complex kinase assay, BK(Ca) channels isolated from rat brain were phosphorylated in the presence of PKC activators, without the addition of exogenous PKC, which suggests that PKC and BK(Ca) channels functionally interact in vivo. Four different PKC isozymes, including PKCdelta, phosphorylated the C-terminus of Slo1 and the addition of purified PKCdelta-activated BK(Ca) channels in excised patches of transfected HEK293 cells. Our results demonstrate that PKC up-regulates BK(Ca) channels and that PKCdelta may functionally interact with BK(Ca) channel complexes in vivo.