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

Abstract

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. 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. 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...