Mitochondrial uncoupler FCCP activates proton conductance but does not block store-operated Ca2+ current in liver cells

Minh Son To, Edoardo C. Aromataris, Joel Castro, Michael L. Roberts, Greg J. Barritt, Grigori Y. Rychkov

Research output: Contribution to journalArticlepeer-review

37 Citations (Scopus)

Abstract

Uncouplers of mitochondrial oxidative phosphorylation, including carbonilcyanide p-triflouromethoxyphenylhydrazone (FCCP) and carbonilcyanide m-cholorophenylhydrazone (CCCP), are widely used in experimental research to investigate the role of mitochondria in cellular function. Unfortunately, it is very difficult to interpret the results obtained in intact cells using FCCP and CCCP, as these agents not only inhibit mitochondrial potential, but may also affect membrane potential and cell volume. Here we show by whole-cell patch clamping that in primary rat hepatocytes and H4IIE liver cells, FCCP induced large proton currents across the plasma membrane, but did not activate any other observable conductance. In intact hepatocytes FCCP inhibits thapsigargin-activated store-operated Ca2+ entry, but in patch clamping under the conditions of strong Ca2+ buffering it has no effect on store-operated Ca2+ current (ISOC). These results indicate that there is no direct connection between mitochondria and activation of ISOC in liver cells and support the notion of indirect regulation of ISOC by mitochondrial Ca2+ buffering.

Original languageEnglish
Pages (from-to)152-158
Number of pages7
JournalArchives of Biochemistry and Biophysics
Volume495
Issue number2
DOIs
Publication statusPublished or Issued - 15 Mar 2010
Externally publishedYes

Keywords

  • FCCP
  • I
  • Liver cells
  • Mitochondria
  • Store-operated Ca channels

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology

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