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

Ross, F. A. et al. (2011) 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. Journal of Biological Chemistry, 286(14), pp. 11929-11936. (doi: 10.1074/jbc.M110.189779) (PMID:21209098) (PMCID:PMC3069395)

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.

• Item Type: Articles
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Rowe, Dr Iain
• Authors: Ross, F. A., Rafferty, J. N., Dallas, M. L., Ogunbayo, O., Ikematsu, N., McClafferty, H., Tian, L., Widmer, H., Rowe, I. C.M., Wyatt, C. N., Shipston, M. J., Peers, C., Hardie, D. G., and Evans, A. M.
• College/School: College of Medical Veterinary and Life Sciences > School of Life Sciences
• Journal Name: Journal of Biological Chemistry
• Publisher: Elsevier
• ISSN: 0021-9258
• ISSN (Online): 1083-351X
• Published Online: 05 January 2011
• Copyright Holders: Copyright © 2011 by The American Society for Biochemistry and Molecular Biology, Inc.
• First Published: First published in Journal of Biological Chemistry 286(14): 11929-11936
• Publisher Policy: Reproduced under a Creative Commons licence