Endothelial Ca2+ signals in Penetrating Arterioles Control Local Blood Flow in the Brain.

Abstract

Cerebral blood flow is exquisitely regulated to meet the fluctuating demands of active neurons. This activity‐dependent increase in blood flow (functional hyperemia) is managed by a number of molecular mechanisms collectively referred to as ‘neurovascular coupling’. Penetrating arterioles—the bridge between pial arteries and deep capillaries—serve as a high‐level control system to regulate local perfusion into the cortex. Here we show that dynamic Ca2+ signals in arteriolar endothelium, consisting of unitary and compound events with distinct spatiotemporal patterning, are dramatically increased by sensory stimulation and are followed by dilation of upstream arterioles and increased RBC flux in downstream capillaries. These arteriolar endothelial Ca2+ signals in the cortical vasculature are dependent on Gq‐protein coupled receptor signaling likely involving prostaglandin E2 (PGE2). PGE2‐dependent activation of EP1 receptors, results in IP3 receptor‐dependent Ca2+ release from the endoplasmic reticulum and Ca2+ entry via TRPV4 channels. Our data highlight the pivotal role of endothelial Ca2+ signals in the regulation of cerebral blood flow.Support or Funding InformationSupported by the National Institutes of Health, Totman Medical Research Trust, Fondation Leducq, EC Horizon 2020.