Role of Calcium Channels in the Protective Effect of Hydrogen Sulfide in Rat Cardiomyoblasts

Background: Hydrogen sulfide contributes to the reduction of oxidative stress-related injury in cardiomyocytes but the underlying mechanism is still unclear. Aims: Here we investigated the role of voltage-operated calcium channels (VOCCs) as mediators of the beneficial effect of H2S against oxidative stress in cultured rat cardiomyoblasts (H9c2). Methods: Intracellular calcium signals were measured by fluorimetric live cell imaging and cell viability by colorimetric assay. Results: Treatment with H2S donor (NaHS 10 mu M) or Nifedipine (10 mu M) decreased resting intracellular calcium concentration [Ca] , suggesting that L-type VOCCs are negatively modulated by H2S. In the presence of Nifedipine H2S was still able to lower [Ca] i, while co-incubation with Nifedipine and Ni2(+) 100 mu M completely prevented H2S-dependent [Ca] i decrease, suggesting that both L-type and T-type VOCCs are inhibited by H2S. In addition, in the same experimental conditions, H2S triggered a slow increase of [Ca] i whose molecular nature remains to be clarified. Pretreatment of H9c2 with NaHS (10 mu M) significantly prevented cell death induced by H2O2. This effect was mimicked by pretreatment with L-Type calcium channel inhibitor Nifedipine (10 mu M). Conclusions: The data provide the first evidence that H2S protects rat cardiomyoblasts against oxidative challenge through the inhibition of L-type calcium channels. Copyright (C) 2014 S. Karger AG, Basel