PubMed 16037691

Referenced in Channelpedia wiki pages of: none

Automatically associated channels: ClvC3 , ClvC4 , Kv2.1

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

Authors: Nobuyuki Takahashi, Xiaoming Wang, Shigeru Tanabe, Hiromi Uramoto, Kouichi Jishage, Shinichi Uchida, Sei Sasaki, Yasunobu Okada

Journal, date & volume: Cell. Physiol. Biochem., 2005 , 15, 263-70

PubMed link:

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.