Hydrogen sulfide activates Ca2+ sparks to induce cerebral arteriole dilatation

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 bymodulating local and global intracellular Ca2+ signals in smooth muscle cells. High-speed confocal imaging revealed that Na2S, an H2S donor, increased Ca2+ spark frequency similar to 1.43-fold and decreased global intracellular Ca2+ concentration ([Ca2+](i)) by similar to 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+ (K-Ca) currents similar to 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 20mM)-induced [Ca2+](i) transients, similar to 1.5-fold. H2S hyperpolarized (by similar to 18 mV) and dilated pressurized (40 mmHg) cerebral arterioles. Iberiotoxin, a KCa channel blocker, reduced H2S-induced hyperpolarization by similar to 51%. Iberiotoxin and ryanodine, a ryanodine receptor channel inhibitor, reduced H2S-induced vasodilatation by similar to 38 and similar to 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.