Effect of hydrogen sulfide on intracellular calcium homeostasis in neuronal cells.

Hydrogen sulfide (H(2)S) is now known as a new biological mediator. In the present study, the effects of H(2)S on intracellular calcium (Ca(2+)) in neuronal SH-SY5Y cells was investigated. In SH-SY5Y neuronal cells, NaHS, a H(2)S donor, concentration-dependently increased Ca(2+). The H(2)S-induced Ca(2+) 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 H(2)S-induced Ca(2+) elevation was found in cells pretreated with combination of all three kinds of inhibitors. Depletion of intracellular Ca(2+) store with thapsigargin or cyclopiazonic acid or blockade of ryanodine receptor with ruthenium red significantly attenuated the effect of H(2)S on Ca(2+). Inhibition of protein kinase A (PKA), phospholipase C (PLC) and protein kinase C (PKC) suppressed the H(2)S-elevated Ca(2+), suggesting that H(2)S may regulate Ca(2+) via both PKA and PLC/PKC pathways. In conclusion, it was found in this study that H(2)S increased Ca(2+) in SH-SY5Y neuronal cells by increasing Ca(2+) influx via plasma membrane and in turn releasing calcium from intracellular calcium store. The findings in the present study provide the direct evidence that H(2)S may serve as a neuromodulator.