TRPV3 Sparklets Mediate Endothelium‐Dependent Dilation of Cerebral Parenchymal Arterioles

Abstract

Elementary Ca2+ influx events through single transient receptor potential vanilliod 4 (TRPV4) channels, called TRPV4 sparklets, mediate endothelium-dependent dilation of mesenteric arteries. TRPV3 channels are present in the cerebral artery endothelium and have a larger unitary conductance and Ca2+ permeability compared with TRPV4 channels. Therefore, we attempted to use total internal reflection fluorescent microscopy (TIRFM) to record TRPV3 sparklets from primary cerebral artery endothelial cells. Carvacrol, a monterpenoid compound derived from oregano, increased the frequency of TRPV3 sparklets in a concentration-dependent manner (EC50 = 8.5 µM). Carvacrol-induced TRPV3 sparklets were inhibited by the selective TRPV3 blocker isopentenyl pyrophosphate (IPP). TRPV3 sparklets have a greater unitary amplitude (ΔF/F0 = 0.20), spatial spread (0.74 µm2), and duration (70 ms) than TRPV4 sparklets, suggesting that TRPV3-mediated Ca2+ influx could have a robust influence on cerebrovascular tone. In pressure myograph experiments, carvacrol caused dilation of cerebral parenchymal arterioles that was blocked by IPP. Carvacrol-induced dilation was also inhibited by block of intermediate and small conductance Ca2+-activated K+ (IK and SK) channels. Together, these data suggest that TRPV3 sparklets cause dilation of cerebral parenchymal arterioles by activating SK and IK channels in the endothelium. Supported by HL091905.