title: The epsilon-isoform of PKC mediates the hypertonic activation of cation channels in confluent monolayers of rat hepatocytes.
abstract: We were interested whether PKC alpha, delta, epsilon or zeta is the isoform actually employed in the activation of hypertonicity-induced cation channels (HICCs) in primary cultures of rat hepatocytes. Quantitative SDS-page and Western-blot experiments revealed that PKC alpha, delta and epsilon were stimulated by Indolactam V (as a DAG substitute for activation of c and nPKCs) but that only PKC delta and epsilon did respond to hypertonic stress. Furthermore, chelation of intracellular Ca(++) by BAPTA-AM did not alter HICC activation in cable-analysis experiments whereas Indolactam V as well as V8 (an Indolactam derivative specific for PKC delta and epsilon) activated HICC currents under isotonic conditions. Finally, by use of Rottlerin (as an inhibitor exhibiting a slight preference for PKC delta over epsilon) PKC epsilon could be identified as the most likely isoform responsible for the activation of the HICC.
authors.affiliation: Department of Systemic Cell Biology, Max-Planck-Institute for Molecular Physiology, Dortmund, Germany.
authors.forename: Katrin
authors.initials: K
authors.lastname: Bierhals
authors.forename: Anna C
authors.initials: AC
authors.lastname: Sondersorg
authors.forename: Chiann-Tso
authors.initials: CT
authors.lastname: Lin
authors.forename: Claudia
authors.initials: C
authors.lastname: Rosenbaum
authors.forename: Herbert
authors.initials: H
authors.lastname: Waldmann
authors.forename: Frank
authors.initials: F
authors.lastname: Wehner
mesh_terms: D000098:Acetophenones / Q000494:pharmacology; D000818:Animals; D001578:Benzopyrans / Q000494:pharmacology; D002478:Cells, Cultured; D004789:Enzyme Activation; D022781:Hepatocytes / Q000187:drug effects / Q000378:metabolism*; D007211:Indoles / Q000494:pharmacology; D007473:Ion Channels / Q000378:metabolism*; D007527:Isoenzymes / Q000378:metabolism; D007769:Lactams / Q000494:pharmacology; D051744:Protein Kinase C-epsilon / Q000378:metabolism*; D051381:Rats
chemical_list: D000098:Acetophenones; D001578:Benzopyrans; D007211:Indoles; D007473:Ion Channels; D007527:Isoenzymes; D007769:Lactams; C043969:indolactam V; C085746:rottlerin; D051744:Protein Kinase C-epsilon