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 BK^{M513I+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 BK^{M513I+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.