Regulation of KCNE1-dependent K+ current by the serum and glucocorticoid-inducible kinase (SGK) isoforms

The slowly activating K+ channel subunit KCNE1 is expressed in a variety of tissues including proximal renal tubules, cardiac myocytes and stria vascularis of inner ear. The present study has been performed to explore whether the serum- and glucocorticoid-inducible kinase family members SGK1, SGK2, or SGK3 and/or protein kinase B (PKB) influence K+ channel activity in Xenopus oocytes expressing KCNE1. cRNA encoding KCNE1 was injected with or without cRNA encoding wild-type SGK1, constitutively active D-S422 SGKI, inactive (K127 N)SGK1, wild-type SGK2, wildtype SGK3 or constitutively active (PKB)-P-T308D,S473D. In oocytes injected with KCNE1 cRNA but not in water-injected oocytes a depolarization from -80 mV to -10 mV led to the appearance of a slowly activating K+ current. Coexpression of SGK1, S422D SGKI, SGK2, SGK3 or (PKB)-P-T308D,S473D but not (K127 N)SGK1 significantly stimulated KCNE1-induced current. The effect did not depend on Na+/K+-ATPase activity. KCNE1-induced current was markedly upregulated by coexpression of KCNQ1 and further increased by additional expression of S422D SGK1, SGK2, SGK3 or (PKB)-P-T308D,S473D. In conclusion, all three members of the SGK family of kinases SGK1-3 and protein kinase B stimulate the slowly activating K+ channel KCNE1/KCNQ1. The kinases may thus participate in the regulation of KCNE1-dependent transport and excitability.