Abstract
We have recently demonstrated that maxi-anion channels constitute a major pathway for the regulated release of ATP. It is widely held that a voltage-dependent anion channel (VDAC) located in the plasmalemma that normally functions in the mitochondrial outer membrane is the most likely candidate protein of this channel. This hypothesis was based on the similarity of shared biophysical properties, such as the large unitary conductance and bell-shaped voltage dependency of the maxi-anion channel and mitochondrial VDAC. In the present study, we deleted each of the three genes encoding the VDAC isoforms individually and collectively. We have demonstrated that maxi-anion channel (around 400 pS) activity in VDAC-deficient mouse fibroblasts was unaltered. The channel activity was similar in VDAC1/VDAC3 double-deficient cells and in double-deficient cells with VDAC2 protein depleted by RNA interference. VDAC deletion slightly down-regulated, but never abolished, the swelling-induced ATP release. The lack of correlation between VDAC protein expression and maxi-anion channel activity strongly argues against the long held hypothesis of plasmalemmal VDAC being the maxi-anion channel. Details of the biophysical profile, such as the different potassium-to-chloride and glutamate-to-chloride selectivity and a different pattern of the voltage-dependent gating provide independent support for our conclusion. [J Physiol Sci. 2006;56 Suppl:S114]
