title: Regulation of KCNE1-dependent K(+) current by the serum and glucocorticoid-inducible kinase (SGK) isoforms.
abstract: 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 (S422D)SGK1, inactive (K127 N)SGK1, wild-type SGK2, wild-type SGK3 or constitutively active (T308D,S473D)PKB. 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)SGK1, SGK2, SGK3 or (T308D,S473D)PKB 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 (T308D,S473D)PKB. 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.
authors.affiliation: Department of Physiology, University of Tübingen, 72076, Tübingen, Germany.
authors.forename: Hamdy M
authors.initials: HM
authors.lastname: Embark
authors.forename: Christoph
authors.initials: C
authors.lastname: Böhmer
authors.forename: Volker
authors.initials: V
authors.lastname: Vallon
authors.forename: Friedrich
authors.initials: F
authors.lastname: Luft
authors.forename: Florian
authors.initials: F
authors.lastname: Lang
mesh_terms: D000818:Animals; D004553:Electric Conductivity; D005260:Female; D006801:Humans; D017874:Immediate-Early Proteins; D051656:KCNQ Potassium Channels; D051657:KCNQ1 Potassium Channel; D009687:Nuclear Proteins; D015221:Potassium Channels / Q000502:physiology*; D024642:Potassium Channels, Voltage-Gated; D020033:Protein Isoforms; D017346:Protein Serine-Threonine Kinases / Q000502:physiology*; D011518:Proto-Oncogene Proteins / Q000502:physiology; D051057:Proto-Oncogene Proteins c-akt; D014982:Xenopus laevis; D000099184:Serum-Glucocorticoid Regulated Kinases
chemical_list: D017874:Immediate-Early Proteins; D051656:KCNQ Potassium Channels; D051657:KCNQ1 Potassium Channel; D009687:Nuclear Proteins; D015221:Potassium Channels; D024642:Potassium Channels, Voltage-Gated; D020033:Protein Isoforms; D017346:Protein Serine-Threonine Kinases; D011518:Proto-Oncogene Proteins; D051057:Proto-Oncogene Proteins c-akt; D000099184:Serum-Glucocorticoid Regulated Kinases; C496909:KCNQ1 protein, human; C059983:potassium channel protein I(sk)