TRPC

Cell biology

Neuroscience

Biology

Endothelial stem cell

Hyperpolarization (physics)

Endocrinology

Receptor

Nuclear magnetic resonance spectroscopy

Signal transduction

Endothelium

Nitric oxide

Biochemistry

Transient receptor potential channel

Vasodilation

Smooth muscle

Organic chemistry

Acetylcholine

In vitro

Glutamate receptor

Internal medicine

TRPV4

Vascular smooth muscle

Medicine

Chemistry

Calcium signaling

TRPC3

International Journal of Molecular Sciences

Background: Neurovascular coupling (NVC) is the mechanism whereby an increase in neuronal activity (NA) leads to local elevation in cerebral blood flow (CBF) to match the metabolic requirements of firing neurons. Following synaptic activity, an increase in neuronal and/or astrocyte Ca2+ concentration leads to the synthesis of multiple vasoactive messengers. Curiously, the role of endothelial Ca2+ signaling in NVC has been rather neglected, although endothelial cells are known to control the vascular tone in a Ca2+-dependent manner throughout peripheral vasculature. Methods: We analyzed the literature in search of the most recent updates on the potential role of endothelial Ca2+ signaling in NVC. Results: We found that several neurotransmitters (i.e., glutamate and acetylcholine) and neuromodulators (e.g., ATP) can induce dilation of cerebral vessels by inducing an increase in endothelial Ca2+ concentration. This, in turn, results in nitric oxide or prostaglandin E2 release or activate intermediate and small-conductance Ca2+-activated K+ channels, which are responsible for endothelial-dependent hyperpolarization (EDH). In addition, brain endothelial cells express multiple transient receptor potential (TRP) channels (i.e., TRPC3, TRPV3, TRPV4, TRPA1), which induce vasodilation by activating EDH. Conclusions: It is possible to conclude that endothelial Ca2+ signaling is an emerging pathway in the control of NVC.

The Role of Endothelial Ca2+ Signaling in Neurovascular Coupling: A View from the Lumen