Activation of protein kinase Calpha couples cell volume to membrane Cl- permeability in HTC hepatoma and Mz-ChA-1 cholangiocarcinoma cells. Hepatology 1998 Oct;28(4):1073-80
Date
10/02/1998Pubmed ID
9755245DOI
10.1002/hep.510280423Scopus ID
2-s2.0-0031688718 (requires institutional sign-in at Scopus site) 49 CitationsAbstract
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 PKC 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 micromol/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.
Author List
Roman RM, Bodily KO, Wang Y, Raymond JR, Fitz JGAuthor
John R. Raymond MD President, CEO, Professor in the President department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
AlkaloidsAnimals
Benzophenanthridines
Bile Duct Neoplasms
Carcinoma, Hepatocellular
Catalytic Domain
Cell Membrane Permeability
Chloride Channels
Chlorides
Cholangiocarcinoma
Culture Media
Enzyme Activation
Humans
Hypotonic Solutions
Isoenzymes
Kinetics
Liver Neoplasms
Liver Neoplasms, Experimental
Membrane Potentials
Patch-Clamp Techniques
Phenanthridines
Protein Kinase C
Protein Kinase C-alpha
Rats
Tumor Cells, Cultured