Selective expression in carotid body type I cells of a single splice variant of the large conductance calcium- and voltage-activated potassium channel confers regulation by AMP-activated protein kinase

F.A. Ross, J.N. Rafferty, M.L. Dallas, O. Ogunbayo, N. Ikematsu, H. McClafferty, L. Tian, H. Widmer, I.C.M. Rowe, C.N. Wyatt, M.J. Shipston, C. Peers, D.G. Hardie, A.M. Evans

Research output: Contribution to journalArticlepeer-review

43 Citations (Scopus)

Abstract

Inhibition of large conductance calcium-activated potassium (BKCa) channels mediates, in part, oxygen sensing by carotid body type I cells. However, BKCa channels remain active in cells that do not serve to monitor oxygen supply. Using a novel, bacterially derived AMP-activated protein kinase (AMPK), we show that AMPK phosphorylates and inhibits BKCa channels in a splice variant-specific manner. Inclusion of the stress-regulated exon within BKCa channel α subunits increased the stoichiometry of phosphorylation by AMPK when compared with channels lacking this exon. Surprisingly, however, the increased phosphorylation conferred by the stress-regulated exon abolished BKCa channel inhibition by AMPK. Point mutation of a single serine (Ser-657) within this exon reduced channel phosphorylation and restored channel inhibition by AMPK. Significantly, RT-PCR showed that rat carotid body type I cells express only the variant of BKCa that lacks the stress-regulated exon, and intracellular dialysis of bacterially expressed AMPK markedly attenuated BKCa currents in these cells. Conditional regulation of BKCa channel splice variants by AMPK may therefore determine the response of carotid body type I cells to hypoxia.
Original languageEnglish
Pages (from-to)11929-11936
Number of pages8
JournalJournal of Biological Chemistry
Volume286
Issue number14
Early online date5 Jan 2011
DOIs
Publication statusPublished - 8 Apr 2011

Fingerprint

Dive into the research topics of 'Selective expression in carotid body type I cells of a single splice variant of the large conductance calcium- and voltage-activated potassium channel confers regulation by AMP-activated protein kinase'. Together they form a unique fingerprint.

Cite this