SGK3 Sensitivity of Large-Conductance Ca2+-Activated K+ Channel.

BACKGROUND/AIMS: Large conductance Ca2+-activated K+ channels (maxi K+ channels or BK channels) are rapidly activated by increase of cytosolic Ca2+ activity. The channels participate in the regulation of diverse functions including neuronal excitation and cell volume. The BK channels may be modified by kinases. Channel regulating kinases include the serum & glucocorticoid inducible kinase 3 (SGK3). The present study explored whether SGK3 modifies the activity of BK channels.

METHODS: cRNA encoding the Ca2+ insensitive BK channel mutant BKM513I+Δ899-903 was injected into Xenopus laevis oocytes without or with additional injection of cRNA encoding wild-type SGK3, constitutively active S419DSGK3, or catalytically inactive K191NSGK3. K+ channel activity was measured utilizing dual electrode voltage clamp.

RESULTS: BK channel activity in BKM513I+Δ899-903 expressing oocytes was significantly increased by co-expression of SGK3 or active S419DSGK3, but not by coexpression of inactive K191NSGK3.

CONCLUSION: SGK3 is a novel positive regulator of BK channels, and thus participates in the regulation of cell volume and excitability.