Hydrogen sulfide activates Ca2+ sparks to induce cerebral arteriole dilatation

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Abstract

Hydrogen sulfide (H2S) is a gaseous vasodilator produced by endothelial cells. Mechanisms by which H2S induces vasodilatation are unclear. We tested the hypothesis that H2S dilates cerebral arterioles by modulating local and global intracellular Ca2+ signals in smooth muscle cells. High-speed confocal imaging revealed that Na2S, an H2S donor, increased Ca2+ spark frequency ∼1.43-fold and decreased global intracellular Ca2+ concentration ([Ca2+]i) by ∼37 nm in smooth muscle cells of intact piglet cerebral arterioles. In contrast, H2S did not alter Ca2+ wave frequency. In voltage-clamped (-40 mV) cells, H2S increased the frequency of iberiotoxin-sensitive, Ca2+ spark-induced transient Ca2+-activated K+ (KCa) currents ∼1.83-fold, but did not alter the amplitude of these events. H2S did not alter the activity of single KCa channels recorded in the absence of Ca2+ sparks in arteriole smooth muscle cells. H2S increased SR Ca2+ load ([Ca2+]SR), measured as caffeine (10 and 20 mm)-induced [Ca2+]i transients, ∼1.5-fold. H2S hyperpolarized (by ∼18 mV) and dilated pressurized (40 mmHg) cerebral arterioles. Iberiotoxin, a KCa channel blocker, reduced H2S-induced hyperpolarization by ∼51%. Iberiotoxin and ryanodine, a ryanodine receptor channel inhibitor, reduced H2S-induced vasodilatation by ∼38 and ∼37%, respectively. In summary, our data indicate that H2S elevates [Ca2+]SR, leading to Ca2+ spark activation in cerebral arteriole smooth muscle cells. The subsequent elevation in transient KCa current frequency leads to membrane hyperpolarization, a reduction in global [Ca2+]i and vasodilatation. © 2012 The Authors. The Journal of Physiological © 2012 The Physiological Society.

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Liang, G. H., Xi, Q., Leffler, C. W., & Jaggar, J. H. (2012). Hydrogen sulfide activates Ca2+ sparks to induce cerebral arteriole dilatation. Journal of Physiology, 590(11), 2709–2720. https://doi.org/10.1113/jphysiol.2011.225128

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