Hydrogen sulfide raises cytosolic calcium in neurons through activation of L-type Ca2+ channels

Hydrogen sulfide (H2S) concentration can be maintained in cell cultures within the range reported for rat brain by repetitive pulses of sodium hydrogen sulfide. Less than 2 h exposure to H2S concentrations within 50 and 120 mu M (i.e., within the upper segment of the reported physiological range of H2S in rat brain), produces a large shift of the intracellular calcium homeostasis in cerebellar granule neurons (CGN) in culture, leading to a large and sustained increase of cytosolic calcium concentration. Only 1 h exposure to H2S concentrations within 100 and 300 mu M raises intracellular calcium to the neurotoxic range, with nearly 50% cell death after 2 h. L-type Ca2+ channels antagonists nimodipine and nifedipine block both the H2S-induced rise of cytosolic calcium and cell death. The N-methyl-D-aspartate receptor antagonists (+)-MK-801 and DL-2-amino-5-phosphonovaleric acid afforded a nearly complete protection against H2S-induced CGN death and largely attenuated the rise of cytosolic calcium. Thus, H2S-induced rise of cytosolic calcium eventually reaches the neurotoxic cytosolic calcium range, leading to glutamate-induced excitotoxic CGN death. The authors conclude that H2S is a major modulator of calcium homeostasis in neurons as it induces activation of Ca2+ entry through L-type Ca2+ channels, and thereby of neuronal activity.