Endothelial signaling at the core of neurovascular coupling: The emerging role of endothelial inward-rectifier K+ (Kir2.1) channels and N-methyl-d-aspartate receptors in the regulation of cerebral blood flow

Int J Biochem Cell Biol. 2021 Jun:135:105983. doi: 10.1016/j.biocel.2021.105983. Epub 2021 Apr 21.

Abstract

Neurovascular coupling (NVC) represents the mechanisms whereby an increase in neuronal activity (NA) may lead to local vasodilation and increase in regional cerebral blood flow (CBF). It has long been thought that neurons and astrocytes generate the vasoactive mediators regulating local changes in CBF, whereas cerebrovascular endothelial cells are not able to directly sense NA. Unexpectedly, recent evidence demonstrated that brain microvascular endothelial cells may sense NA through inward-rectifier K+ (Kir2.1) channels and may detect synaptic activity via N-methyl-d-aspartate (NMDA) receptors (NMDARs). In the present perspective, therefore, we discuss the hypothesis that endothelial Kir2.1 channels and NMDARs play a key role in NVC and in CBF regulation, which is crucial to unravel the cellular and molecular underpinnings of blood oxygen level-dependent signals.

Keywords: Cerebral blood flow; Cerebrovascular endothelial cells; G(q)PCRs; K(ir)2.1 channels; NMDA receptors; Neurovascular coupling; TRPV4 channel.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Brain / blood supply*
  • Cerebrovascular Circulation*
  • Endothelial Cells / metabolism*
  • Humans
  • Neurovascular Coupling*
  • Potassium Channels, Inwardly Rectifying / metabolism*
  • Receptors, N-Methyl-D-Aspartate / metabolism*
  • Signal Transduction

Substances

  • Potassium Channels, Inwardly Rectifying
  • Receptors, N-Methyl-D-Aspartate