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Hydrogen sulfide activates Ca 2+ sparks to induce cerebral arteriole dilation
Author(s) -
Liang Guo Hua,
Xi Qi,
Leffler Charles W.,
Jaggar Jonathan H.
Publication year - 2012
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.26.1_supplement.870.20
Subject(s) - ryanodine receptor , arteriole , vasodilation , chemistry , iberiotoxin , vascular smooth muscle , biophysics , medicine , intracellular , nicardipine , carbenoxolone , endocrinology , myogenic contraction , calcium , smooth muscle , gap junction , biochemistry , microcirculation , biology
Hydrogen sulfide (H 2 S) is a gaseous vasodilator produced by endothelial cells. Mechanisms by which H 2 S induce vasodilation are unclear. We tested the hypothesis that H 2 S dilates piglet cerebral arterioles by modulating local and global intracellular Ca 2+ signals in smooth muscle cells. High‐speed confocal imaging revealed that H 2 S increased Ca 2+ spark frequency ~1.43 fold and decreased global intracellular Ca 2+ concentration ([Ca 2+ ] i ) by ~37 nM in smooth muscle cells of intact cerebral arteries. In contrast, H 2 S did not alter Ca 2+ wave frequency. In voltage‐clamped (–40 mV) cells, H 2 S increased the frequency of Ca 2+ spark‐induced transient Ca 2+ ‐activated K + (K Ca ) currents ~1.8 fold, but did not alter the amplitude of these events. H 2 S did not alter the activity of single K Ca channels recorded in the absence of Ca 2+ sparks in arteriole smooth muscle cells. H 2 S increased SR Ca 2+ load ([Ca 2+ ] SR ), measured as caffeine (10 mM)‐induced [Ca 2+ ] i transients, ~1.5 fold. H 2 S dilated pressurized cerebral arterioles. Iberiotoxin, a K Ca channel blocker, and ryanodine, a ryanodine receptor (RyR) channel inhibitor, reduced H 2 S‐induced vasodilation by ~38 and ~37%, respectively. In summary, our data indicate that H 2 S elevates [Ca 2+ ] SR , leading to Ca 2+ spark activation in cerebral arteriole smooth muscle cells. The subsequent elevation in transient K Ca current frequency leads to a reduction in global [Ca 2+ ] i and vasodilation. NIH/NHLBI