Cytosolic Ca2+ and protein kinase Calpha couple cellular metabolism to membrane K+ permeability in a human biliary cell line

The Journal of Clinical Investigation
Y WangJ G Fitz

Abstract

Cholangiocytes represent an important target of injury during the ischemia and metabolic stress that accompanies liver preservation. Since K+ efflux serves to minimize injury during ATP depletion in certain other cell types, the purpose of these studies was to evaluate the effects of ATP depletion on plasma membrane K+ permeability of Mz-ChA-1 cells, a model human biliary cell line. Cells were exposed to dinitrophenol (50 microM) and 2-deoxyglucose (10 mM) as the standard model of metabolic injury. Whole-cell and single K+ channel currents were measured using patch clamp techniques; and intracellular [Ca2+] ([Ca2+]i) was estimated by calcium green-1 fluorescence. Metabolic stress increased [Ca2+]i, and stimulated translocation of the alpha isoform of protein kinase C (PKCalpha) from cytosolic to particulate cell fractions. The same maneuver increased membrane K+ permeability 40-70-fold as detected by (a) activation of K+selective whole cell currents of 2,176+/-218 pA (n = 34), and (b) opening of apamin-sensitive K+ channels with a unitary conductance of 17.0+/-0.2 pS. PKCalpha translocation and channel opening appear to be related since stress-induced K+ efflux is inhibited by chelation of cytosolic Ca2+, exposure to the PKC in...Continue Reading

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Citations

Oct 2, 1998·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·R M RomanJ G Fitz
Aug 22, 2000·Journal of Hepatology·A P FeranchakR M Roman
Aug 22, 2000·Journal of Hepatology·J A Dranoff, M H Nathanson
May 16, 1998·Trends in Microbiology·A Casadevall
Oct 30, 2012·American Journal of Physiology. Gastrointestinal and Liver Physiology·Amal K DuttaAndrew P Feranchak
Oct 23, 2010·American Journal of Physiology. Gastrointestinal and Liver Physiology·A LoganathanG I Sandle
Sep 13, 2008·American Journal of Physiology. Gastrointestinal and Liver Physiology·Amal K DuttaAndrew P Feranchak
Apr 12, 2000·Critical Reviews in Oral Biology and Medicine : an Official Publication of the American Association of Oral Biologists·J E Melvin
Nov 8, 2003·American Journal of Physiology. Gastrointestinal and Liver Physiology·David GatofJ Gregory Fitz
Nov 7, 2015·American Journal of Physiology. Gastrointestinal and Liver Physiology·Amal K DuttaAndrew P Feranchak
Feb 25, 2020·American Journal of Physiology. Gastrointestinal and Liver Physiology·Amal K DuttaAndrew P Feranchak
Feb 19, 2010·Journal of Virology·Nishi R SharmaDebi P Sarkar
Jun 3, 1999·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·J P HattonD Schmitt
Jun 16, 2001·American Journal of Physiology. Renal Physiology·Z X LiuL G Cantley
Mar 14, 2001·American Journal of Physiology. Cell Physiology·E T BarfodS D Lidofsky
Dec 26, 2001·American Journal of Physiology. Gastrointestinal and Liver Physiology·Richard RomanJ Gregory Fitz
Dec 13, 2005·American Journal of Physiology. Cell Physiology·Barbara A KlarlFlorian Lang
May 27, 2010·American Journal of Physiology. Gastrointestinal and Liver Physiology·Amal K DuttaAndrew P Feranchak

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