Protein kina8e c modulates a swelling-activated cl- channel in htc rat hepatoma cells

K. Bodily, J. G. Fitz

Research output: Contribution to journalArticle

Abstract

Hepatocytes exhibit facilitated uptake of organic and inorganic solutes which impose osmotic demands resulting in cell swelling. Cell volume recovery depends upon solute efflux mediated in part by activation of Cl- channels (Icl-swell) but the mechanisms coupling cell volume to channel opening are unknown. These studies used whole cell patch clamp techniques to characterize the properties and regulation of Icl-swell in HTC cells. Intracellular perfusion with hypertonic sucrose-containing buffer activated anion-selective currents with outward rectification, time-dependent inactivation, and reversal potentials near Ecl. Incremental increases in intracellular osmolality through addition of 20-100 mM sucrose caused a concentration-dependent increase in Icl-swell ranging from -3.4±0.9 to -69.9±11.2 pA/pF at -80 mV. Perfusion with Ca++-free intracellular buffer (2 mM EGTA) markedly reduced Icl-swelln (-3.7+0.6 pA/pF, p<0.01) from control values (-35.6+8.8 pA/pF). Inhibition of protein kinase C (PKC) by 25 MM chelerythrine decreased Icl-swell (-3.5+0.6 pA/pF, p<0.01), while preactivation of PKC with 2 /iM 4 beta-phorbol 12-myristate, 13-acetate (PMA) modestly increased currents (-47.3±21.8 pA/pF, p=0.69). These studies demonstrate that changes in cell volume are closely coupled to membrane Cl- permeability and suggest that activation of Cl- channels contributing to Icl-swell depends on both Ca++ and PKC-dependent pathways.

Original languageEnglish (US)
Pages (from-to)299a
JournalJournal of Investigative Medicine
Volume44
Issue number3
StatePublished - Jan 1 1996

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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