AJP - Gastrointestinal and Liver Physiology, Vol 270, Issue 2 307-G313, Copyright © 1996 by American Physiological Society

ARTICLES

ATP-induced rise in apamin-sensitive Ca(2+)-dependent K+ conductance in adult rat hepatocytes

Y. Yamashita, H. Ogawa and N. Akaike
Department of Physiology, Kyushu University Faculty of Medicine, Fukuoka, Japan.

Exogenous ATP-induced transient outward currents (IATP) were investigated in isolated adult rat hepatocytes using conventional whole cell patch and nystatin perforated patch recording modes. The IATP increased in a sigmoidal fashion with an increase in ATP concentration, where the half-maximal concentration was 1.4 microM. The order of current potency was 2-methylthio-ATP > or = UTP = ATP > > alpha, beta-methylene-ATP. IATP was depressed in a concentration-dependent manner by suramin and apamin. IATP reversed its direction at the K+ equilibrium potential. IATP occurred easily in hepatocytes obtained from female rats weighing > 250 g. Removal of extracellular Ca2+ had no effect on the peak amplitude of IATP, but thapsigargin abolished it. Intracellular perfusion with 1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid, heparin, guanosine 5'-O-(3-thiotriphosphate), or neomycin also abolished IATP. Pretreatment with pertussis toxin or calmodulin antagonists had no effect on IATP. It was concluded that ATP binding to both P2Y and P2U purinoceptors coupled to G protein may raise apaminsensitive Ca(2+)-dependent K+ conductance via a phospholipase C-inositol trisphosphate-Ca2+ signaling pathway.

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