Transfection of a phosphatidyl-4-phosphate 5-kinase gene into rat atrial myocytes removes inhibition of GIRK current by endothelin and alpha-adrenergic agonists.
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).
Bender
Kirsten
K
Department of Physiology, Ruhr-University Bochum, D-4480 Bochum, Germany.
Wellner-Kienitz
Marie-Cécile
MC
Pott
Lutz
L
D000316:Adrenergic alpha-Agonists / Q000494:pharmacology*; D000818:Animals; D019332:Endothelin-1 / Q000494:pharmacology*; D005260:Female; D006325:Heart Atria / Q000378:metabolism*; D008297:Male; D017853:Phosphotransferases (Alcohol Group Acceptor) / Q000235:genetics*; D026902:Potassium Channel Blockers; D051381:Rats; D011921:Rats, Inbred WKY; D014162:Transfection
D000316:Adrenergic alpha-Agonists; D019332:Endothelin-1; D026902:Potassium Channel Blockers; D017853:Phosphotransferases (Alcohol Group Acceptor); C020077:1-phosphatidylinositol-4-phosphate 5-kinase