P6 Hydrogen sulfide activates Ca²⁺ sparks to induce cerebral arteriole dilation

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• 作者：Guohua Liang ; Qi xi ; Charles Leffler ; Jonathan Jaggar
• 刊名：Nitric Oxide
• 出版年：2012
• 出版时间：15 September, 2012
• 年：2012
• 卷：27
• 期：supp_S2
• 页码：S13-S14
• 全文大小：1K

文摘

Hydrogen sulfide (H₂S) is a gaseous vasodilator produced by endothelial cells. Mechanisms by which H₂S induce vasodilation are unclear. We tested the hypothesis that H₂S dilates piglet cerebral arterioles by modulating local and global intracellular Ca²⁺ signals in smooth muscle cells. High-speed confocal imaging revealed that H₂S increased Ca²⁺ spark frequency ¡«1.43-fold and decreased global intracellular Ca²⁺ concentration ([Ca²⁺]_i) by ¡«37 nM in smooth muscle cells of intact cerebral arteries. In contrast, H₂S did not alter Ca²⁺ wave frequency. In voltage-clamped (?40 mV) cells, H₂S increased the frequency of Ca²⁺ spark-induced transient Ca²⁺-activated K⁺ (K_Ca) currents  ¡« 1.8-fold, but did not alter the amplitude of these events. H₂S did not alter the activity of single K_Ca channels recorded in the absence of Ca²⁺ sparks in arteriole smooth muscle cells. H₂S increased SR Ca²⁺ load ([Ca²⁺]_SR), measured as caffeine (10 mM)-induced [Ca²⁺]_i transients, ¡«1.5-fold. H₂S dilated pressurized cerebral arterioles. Iberiotoxin, a K_Ca channel blocker, and ryanodine, a ryanodine receptor (RyR) channel inhibitor, reduced H₂S-induced vasodilation 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 K_Ca current frequency leads to a reduction in global [Ca²⁺]_i and vasodilation.