Activation of protein kinase Cα couples cell volume to membrane Cl- permeability in HTC hepatoma and Mz-ChA-1 cholangiocarcinoma cells

Richard M. Roman, Kurt O. Bodily, Yu Wang, John R. Raymond, J. Gregory Fitz

Research output: Contribution to journalArticlepeer-review

47 Scopus citations

Abstract

Physiological increases in liver cell volume lead to an adaptive response that includes opening of membrane Cl- channels, which is critical for volume recovery. The purpose of these studies was to assess the potential role for protein kinase C (PKC) as a signal involved in cell volume homeostasis. Studies were performed in HTC rat hepatoma and Mz-ChA-1 human cholangiocarcinoma cells, which were used as model hepatocytes and cholangiocytes, respectively. In each cell type, cell volume increases were followed by: 1) translocation of PKCα from cytosolic to particulate (membrane) fractions; 2) a 10- to 40-fold increase in whole-cell membrane Cl- current density; and 3) partial recovery of cell volume. In HTC cells, the volume-dependent Cl- current response (-46 ± 5 pA/pF) was inhibited by down-regulation of PKC (100 nmol/L phorbol 12-myristate 13-acetate for 18 hours [PMA]; -1.97 ± 1.5 pA/pF), chelation of cytosolic Ca2+ (2 mmol/L EGTA; -5.3 ± 4.0 pA/pF), depletion of cytosolic adenosine triphosphate (ATP) (3 U/mL apyrase; -12.58 ± 1.45 pA/pF), and by the putative PKC inhibitor, chelerythrine (25 μmol/L; -7 ± 3 pA/pF). In addition, PKC inhibition by chelerythrine and calphostin C (500 nmol/L) prevented cell volume recovery from swelling. Similar results were obtained in Mz-ChA-1 biliary cells. These findings indicate that swelling-induced activation of PKC represents an important signal coupling cell volume to membrane Cl- permeability in both hepatic and biliary cell models.

Original languageEnglish (US)
Pages (from-to)1073-1080
Number of pages8
JournalHepatology
Volume28
Issue number4 I
DOIs
StatePublished - 1998

ASJC Scopus subject areas

  • Hepatology

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