Ca2+-mediated potentiation of the swelling-induced taurine efflux from HeLa cells: on the role of calmodulin and novel protein kinase C isoforms

J Membr Biol. 2004 Sep 15;201(2):59-75. doi: 10.1007/s00232-004-0705-6.

Abstract

The present work sets out to investigate how Ca(2+) regulates the volume-sensitive taurine-release pathway in HeLa cells. Addition of Ca(2+)-mobilizing agonists at the time of exposure to hypotonic NaCl medium augments the swelling-induced taurine release and subsequently accelerates the inactivation of the release pathway. The accelerated inactivation is not observed in hypotonic Ca(2+)-free or high-K(+) media. Addition of Ca(2+)-mobilizing agonists also accelerates the regulatory volume decrease, which probably reflects activation of Ca(2+)-activated K(+) channels. The taurine release from control cells and cells exposed to Ca(2+) agonists is equally affected by changes in cell volume, application of DIDS and arachidonic acid, indicating that the volume-sensitive taurine leak pathway mediates the Ca(2+)-augmented taurine release. Exposure to Ca(2+)-mobilizing agonists prior to a hypotonic challenge also augments a subsequent swelling-induced taurine release even though the intracellular Ca(2+)-concentration has returned to the unstimulated level. The Ca(2+)-induced augmentation of the swelling-induced taurine release is abolished by inhibition of calmodulin, but unaffected by inhibition of calmodulin-dependent kinase II, myosin light chain kinase and calcineurin. The effect of Ca(2+)-mobilizing agonists is mimicked by protein kinase C (PKC) activation and abolished in the presence of the PKC inhibitor Gö6850 and following downregulation of phorbol ester-sensitive PKC isoforms. It is suggested that Ca(2+) regulates the volume-sensitive taurine-release pathway through activation of calmodulin and PKC isoforms belonging to the novel subclass (nPKC).

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Calcium / metabolism*
  • Calcium Signaling / physiology*
  • Calmodulin / metabolism*
  • Cell Size
  • Enzyme Inhibitors / pharmacology
  • HeLa Cells
  • Humans
  • Hypotonic Solutions
  • Indoles / pharmacology
  • Isoenzymes / metabolism
  • Maleimides / pharmacology
  • Protein Kinase C / metabolism*
  • Taurine / metabolism*

Substances

  • Calmodulin
  • Enzyme Inhibitors
  • Hypotonic Solutions
  • Indoles
  • Isoenzymes
  • Maleimides
  • Taurine
  • Protein Kinase C
  • bisindolylmaleimide I
  • Calcium