Acidosis Dilates Brain Parenchymal Arterioles by Conversion of Calcium Waves to Sparks to Activate BK Channels

作者：Dabertrand Fabrice; Nelson Mark T; Brayden Joseph E^*

来源：Circulation Research, 2012, 110(2): 285-294.

DOI：10.1161/CIRCRESAHA.111.258145

• brain parenchymal arteriole
• acidosis
• Ca2+ sparks
• ryanodine receptor
• potassium channel

Rationale: Acidosis is a powerful vasodilator signal in the brain circulation. However, the mechanisms by which this response occurs are not well understood, particularly in the cerebral microcirculation. One important mechanism to dilate cerebral (pial) arteries is by activation of large-conductance, calcium-sensitive potassium (BKCa) channels by local Ca2+ signals (Ca2+ sparks) through ryanodine receptors (RyRs). However, the role of this pathway in the brain microcirculation is not known. %26lt;br%26gt;Objective: The objectives of this study were to determine the mechanism by which acidosis dilates brain parenchymal arterioles (PAs) and to elucidate the roles of RyRs and BKCa channels in this response. %26lt;br%26gt;Methods and Results: Internal diameter and vascular smooth muscle cell Ca2+ signals were measured in isolated pressurized murine PAs, using imaging techniques. In physiological pH (7.4), vascular smooth muscle cells exhibited primarily RyR-dependent Ca2+ waves. Reducing external pH from 7.4 to 7.0 in both normocapnic and hypercapnic conditions decreased Ca2+ wave activity, and dramatically increased Ca2+ spark activity. Acidic pH caused a dilation of PAs which was inhibited by about 60% by BKCa channel or RyR blockers, in a nonadditive manner. Similarly, dilator responses to acidosis were reduced by nearly 60% in arterioles from BKCa channel knockout mice. Dilations induced by acidic pH were unaltered by inhibitors of K-ATP channels or nitric oxide synthase. %26lt;br%26gt;Conclusions: These results support the novel concept that acidification, by converting Ca2+ waves to sparks, leads to the activation of BKCa channels to induce dilation of cerebral PAs. (Circ Res. 2012;110:285-294.)

• 出版日期2012-1-20