Figure 1. Effect of pH on RyR-mediated Ca²⁺ signals in smooth muscle cells of pressurized pial arteries and parenchymal arterioles.

By modulating RyR excitability, protons can influence the shape of the Ca²⁺ signals in cerebrovascular smooth muscle cells. At the physiologic pH of cerebrospinal fluid (pH=7.3) myocytes in large (pial) arteries display spatially limited and brief Ca²⁺ release events (sparks). When pH increases (alkalosis), RyR open probability (P_o) increases as well and the Ca²⁺ ions released by a cluster of RyRs activate neighboring clusters, forming a Ca²⁺ wave by propagation of the signal. In contrast, parenchymal arterioles display Ca²⁺ waves under normal conditions. When pH decreases (acidosis), RyR P_o is low and this spatially restricts the Ca²⁺ release (Ca²⁺ spark). This reshaping of Ca²⁺ signals in the brain microcirculation plays a fundamental role during the vasodilation induced by acidosis.