4.5 Article

Transfection of a phosphatidyl-4-phosphate 5-kinase gene into rat atrial myocytes removes inhibition of GIRK current by endothelin and α-adrenergic agonists

Journal

FEBS LETTERS
Volume 529, Issue 2-3, Pages 356-360

Publisher

ELSEVIER SCIENCE BV
DOI: 10.1016/S0014-5793(02)03426-9

Keywords

cardiac myocyte; G protein-activated inward rectifying K+ channel; PIP2; adrenergic receptor; endothelin; muscarinic receptor

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GIRK (G protein-activated inward-rectifying K+ channel) channels, important regulators of membrane excitability in the heart and in the central nervous, are activated by interaction with betagamma subunits from heterotrimeric G proteins upon receptor stimulation. For activation interaction of the channel with phosphatidylinositol 4,5-bisphosphate (PtIns(4,5)P-2) is conditional. Previous studies have provided evidence that in myocytes PtIns(4,5)P-2 levels relevant to GIRK channel regulation are under regulatory control of receptors activating phospholipase C. In the present study a phosphatidyl-4-phosphate 5-kinase was expressed in atrial myocytes by transient transfection. This did not affect basal properties of GIRK current activated by acetylcholine via M-2 receptors but completely abolished inhibition of guanosine triphosphate-gamma-S activated current by endothelin-1 or alpha-adrenergic agonists. We conclude that though PtIns(4,5)P-2 is conditional for channel gating, its normal level in the membrane is not limiting basal function of GIRK channels. Moreover, our data provide further evidence for a regulation of GIRK channels by alpha(1A) receptors and endothelin-A receptors, endogenously expressed in atrial myocytes, via depletion of PtIns(4,5)P-2. (C) 2002 Federation of European Biochemical Societies. Published by Elsevier Science B.V. All rights reserved.

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