ClC-3-independent sensitivity of apoptosis to Cl- channel blockers in mouse cardiomyocytes

Cell Physiol Biochem. 2005;15(6):263-70. doi: 10.1159/000087236.

Abstract

It has been shown that Cl-/HCO3- exchangers and Cl- channels, both of which are sensitive to stilbene derivatives, have essential roles in the mechanism of apoptosis induction. Staurosporine-induced apoptosis in neonatal mouse cardiomyocytes was prevented by a stilbene derivative, DIDS. To clarify whether Cl-/HCO3- exchangers or Cl- channels are targets of DIDS and whether ClC-3 is involved in the apoptotic process, staurosporine-induced reduction of cell viability, DNA laddering and caspase-3 activation were examined in cultured mouse ventricular myocytes derived from wild-type and ClC-3-deficient mice. Staurosporine-induced apoptosis and its DIDS sensitivity in ambient HCO3(-)-free conditions in which operation of Cl-/HCO3- exchangers is minimized were indistinguishable from when HCO3- was present. Apoptosis was also prevented by application of a non-stilbene-derivative Cl- channel blocker, NPPB, which cannot block Cl-/HCO3- exchangers. Cardiomyocytes derived from ClC-3-deficient mice similarly underwent apoptosis after exposure to staurosporine; moreover, apoptosis was prevented by application of DIDS or NPPB. Thus, we conclude that in cardiomyocytes, apoptosis is critically dependent on operation not of Cl-/HCO3- exchangers but of Cl- channels which are distinct from ClC-3.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis / drug effects*
  • Apoptosis / physiology
  • Chloride Channels / antagonists & inhibitors
  • Chloride Channels / physiology*
  • Mice
  • Myocardium / cytology*
  • Staurosporine / pharmacology

Substances

  • Chloride Channels
  • ClC-3 channel
  • Staurosporine