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Regulation of cation channels in liver cells by intracellular calcium and protein kinase C.

Publication ,  Journal Article
Fitz, JG; Sostman, AH; Middleton, JP
Published in: Am J Physiol
April 1994

The regulation of Ca(2+)-permeant cation channels in HTC hepatoma cells was investigated using patch clamp and fluorescence techniques. In intact cells, exposure to nucleotide analogues ATP, uridine 5'-triphosphate (UTP), and adenosine 5'-O-(3-thiotriphosphate) (ATP gamma S) caused transient opening of channels with linear conductances of approximately 18 and approximately 28 pS. Channels were permeable to Na+, K+, and Ca2+ and carried inward (depolarizing) current at the resting potential. Exposure to thapsigargin to increase cytosolic Ca2+ concentration ([Ca2+]i) opened similar channels, suggesting that opening is stimulated by a rise in [Ca2+]i. In subconfluent monolayers, ATP increased [Ca2+]i with half-maximal effects at approximately 7.4 microM; at 10(-4) M, the peak increase in [Ca2+]i was ATP > UTP > ATP gamma S >> 2-methylthioadenosine 5'-triphosphate, alpha,beta-methyleneadenosine 5'-triphosphate, and adenosine. The relative potency suggests that the effects are mediated by 5'-nucleotide receptors. In excised inside-out patches, channels were not activated by myo-inositol 1,4,5-trisphosphate (50-100 microM) or myo-inositol 1,3,4,5-trisphosphate (20 microM) but opened after increases in Ca2+ to greater than approximately 250 nM, consistent with a direct role for Ca2+ in channel opening. In intact cells, channel opening was followed by a prolonged refractory period. Protein kinase C appears to contribute by inhibition of the ATP-stimulated [Ca2+]i response and by direct inhibitory effects on the channel. These findings indicate that extracellular ATP leads to modulation of liver cell cation channels through activation of 5'-nucleotide receptors and are consistent with a model in which transient opening of channels is stimulated by a rise in [Ca2+]i and subsequent closure is mediated by protein kinase C-dependent pathways.

Duke Scholars

Published In

Am J Physiol

DOI

ISSN

0002-9513

Publication Date

April 1994

Volume

266

Issue

4 Pt 1

Start / End Page

G677 / G684

Location

United States

Related Subject Headings

  • Tumor Cells, Cultured
  • Rats
  • Protein Kinase C
  • Osmolar Concentration
  • Nucleotides
  • Liver
  • Ion Channels
  • Intracellular Membranes
  • Extracellular Space
  • Cations
 

Citation

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Fitz, J. G., Sostman, A. H., & Middleton, J. P. (1994). Regulation of cation channels in liver cells by intracellular calcium and protein kinase C. Am J Physiol, 266(4 Pt 1), G677–G684. https://doi.org/10.1152/ajpgi.1994.266.4.G677
Fitz, J. G., A. H. Sostman, and J. P. Middleton. “Regulation of cation channels in liver cells by intracellular calcium and protein kinase C.Am J Physiol 266, no. 4 Pt 1 (April 1994): G677–84. https://doi.org/10.1152/ajpgi.1994.266.4.G677.
Fitz JG, Sostman AH, Middleton JP. Regulation of cation channels in liver cells by intracellular calcium and protein kinase C. Am J Physiol. 1994 Apr;266(4 Pt 1):G677–84.
Fitz, J. G., et al. “Regulation of cation channels in liver cells by intracellular calcium and protein kinase C.Am J Physiol, vol. 266, no. 4 Pt 1, Apr. 1994, pp. G677–84. Pubmed, doi:10.1152/ajpgi.1994.266.4.G677.
Fitz JG, Sostman AH, Middleton JP. Regulation of cation channels in liver cells by intracellular calcium and protein kinase C. Am J Physiol. 1994 Apr;266(4 Pt 1):G677–G684.

Published In

Am J Physiol

DOI

ISSN

0002-9513

Publication Date

April 1994

Volume

266

Issue

4 Pt 1

Start / End Page

G677 / G684

Location

United States

Related Subject Headings

  • Tumor Cells, Cultured
  • Rats
  • Protein Kinase C
  • Osmolar Concentration
  • Nucleotides
  • Liver
  • Ion Channels
  • Intracellular Membranes
  • Extracellular Space
  • Cations