Effect of hydrogen sulfide on intracellular calcium homeostasis in neuronal cells

Hydrogen sulfide (H2S) is now known as a new biological mediator. In the present study, the effects of H2S on intracellular calcium ([Ca2+](i)) in neuronal SH-SY5Y cells was investigated. In SH-SY5Y neuronal cells, NaHS, a H2S donor, concentration-dependently increased [Ca2+](i). The H2S-induced Ca2+ elevation was significantly attenuated by EGTA-treated calcium-free Krebs' solution. This elevation was also reduced by antagonists of L-type (verapamil and nifedipine), T-type (mibefradil) calcium channels and N-methyl-D-aspartate receptor (MK-801, AP-5 and ifenprodil). A 90% reduction in H2S-induced [Ca2+](i), elevation was found in cells pretreated with combination of all three kinds of inhibitors. Depletion of intracellular Ca2+ store with thapsigargin or cyclopiazonic acid or blockade of ryanodine receptor with ruthenium red significantly attenuated the effect of H2S on [Ca2+](i). Inhibition of protein kinase A (PKA), phospholipase C (PLC) and protein kinase C (PKC) suppressed the H2S-elevated [Ca2+](i), suggesting that H2S may regulate [Ca2+](i) via both PKA and PLC/PKC pathways. In conclusion, it was found in this study that H2S increased [Ca2+](i), in SH-SY5Y neuronal cells by increasing Ca2+ influx via plasma membrane and in turn releasing calcium from intracellular calcium store. The findings in the present study provide the direct evidence that H2S may serve as a neuromodulator. (C) 2009 Elsevier Ltd. All rights reserved.