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Neurochem Int. 2010 Feb;56(3):508-15. doi: 10.1016/j.neuint.2009.12.011. Epub 2009 Dec 22.

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

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  • 1Department of Pharmacology, Yong Loo Lin School of Medicine, National University of Singapore, 10 Medical Drive, Singapore.


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+)](i)) in neuronal SH-SY5Y cells was investigated. In SH-SY5Y neuronal cells, NaHS, a H(2)S donor, concentration-dependently increased [Ca(2+)](i). 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+)](i) 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+)](i). Inhibition of protein kinase A (PKA), phospholipase C (PLC) and protein kinase C (PKC) suppressed the H(2)S-elevated [Ca(2+)](i), suggesting that H(2)S may regulate [Ca(2+)](i) via both PKA and PLC/PKC pathways. In conclusion, it was found in this study that H(2)S increased [Ca(2+)](i) 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.

Copyright (c) 2009 Elsevier Ltd. All rights reserved.

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