Hydrogen peroxide modulates whole cell Ca2+ currents through L-type channels in cultured rat dentate granule cells

Modification of voltage-gated Ca2+ channels by hydrogen peroxide, a membrane-permeable form of reactive oxygen species, in cultured dentate granule cells was examined using the whole cell patch clamp technique. Pretreatment with hydrogen peroxide (1 and 10 muM) for 2 h enhanced the Ca2+ current without affecting its voltage dependence. The enhancement was completely cancelled by 1 mM glutathione, an antioxidant, and 2 muM nifedipine, an L-type Ca2+ channel blocker. In contrast, the enhancement of the Ca2+ current was not mimicked by pretreatment with 10 mug/ml tunicamycin, an endoplasmic reticulum stressor. These results suggest that oxidative stress induced by hydrogen peroxide selectively regulates the activity of L-type Ca2+ channels. (C) 2003 Elsevier Ireland Ltd. All rights reserved.