Hydrogen sulfide regulates cardiac sarcoplasmic reticulum Ca(2+) uptake via K(ATP) channel and PI3K/Akt pathway.

Hydrogen sulfide regulates cardiac sarcoplasmic reticulum Ca(2+) uptake via K(ATP) channel and PI3K/Akt pathway.

Life Sci. 2012 Aug 2;

Authors: Chen Y, Zhao J, Du J, Xu G, Tang C, Geng B

Abstract
AIMS: To investigate the effects of hydrogen sulfide (H(2)S) on calcium uptake activity of the rat cardiac sarcoplasmic reticulum (SR) and possible signaling. MAIN METHODS: Crude SR was isolated after treatment with H(2)S, then SR Ca(2+) uptake and SR Ca(2+)-ATPase (SERCA) activity was measured by the isotopic tracer method. The possible roles of the K(ATP) channel and PI3K/Akt and SR-membrane protein phospholamban (PLB) pathway were analyzed by specific blockers, and target protein activation was assayed by measuring protein phosphorylation. KEY FINDINGS: Exogenous H(2)S lowered Ca(2+) uptake into the SR time or concentration dependently, which was associated with decreased SERCA activity. Inhibiting endogenous H(2)S production by DL-propargylglycine increased SR Ca(2+) uptake and SERCA activity. H(2)S inhibition of PLB phosphorylation was through SERCA activity and was reversed by two PI3K inhibitors, wortmannin and LY294002. Glibenclamide (a K(ATP) channel blocker) blocked the inhibitory effects of H(2)S on PLB and Akt phosphorylation. Pinacidil (a K(ATP) channel opener) reduced the phosphorylation of PLB and reversed the effects of DL-propargylglycine. H(2)S preconditioning increased PLB phosphorylation but did not affect SERCA activity. SIGNIFICANCE: Endogenous H(2)S transiently and reversibly inhibits SR Ca(2+) uptake in rat heart SR because of downregulated SERCA activity associated with PLB phosphorylation by the PI3K/Akt or K(ATP) channel. The transient negative regulation of SR Ca(2+) uptake and the L-type Ca(2+) channel contributes to Ca(2+) cycle homeostasis, which might be an important molecular mechanism in ischemic diseases.

PMID: 22884808 [PubMed - as supplied by publisher]

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