TRPA1 channel: New kid in the 'neurovascular coupling' town

Abstract

The just-in time delivery of oxygen and nutrients to active brain regions to support function (functional hyperemia; FH) is mediated by not yet fully understood mechanisms collectively referred to as 'neurovascular coupling' (NVC). In a recent publication (eLife 2021) Thakore et al. provide profound mechanistic insight how the capillary endothelial transient receptor potential ankyrin 1 (TRPA1) channel contribute to blood flow control and functional hyperemia in the brain.

Keywords: Calcium signaling; Capillary endothelium; Cerebral blood flow; Functional hyperemia; Neurovascular coupling; TRPA1 channels.

Figure 1.

Biphasic model of conducting vasodilation following activation of capillary endothelial TRPA1 channels proposed by Thakore et al. A. Schematic diagram of a brain section illustrating the microvascular preparations used for this study: obtained from the subcortical region supplied by the middle cerebral artery (MCA). B. Magnification of inset depicted in A. The authors propose that activation of TRPA1 channels in capillary endothelial cells (cECs) generates an electrical signal (Ca²⁺ wave) that slowly propagates through the capillary network, and it subsequently converts into a faster propagation hyperpolarizing signal when reaches the post–arteriole (pericyte–covered) transitional segment. C. Detailed molecular mechanisms of the slow and rapid phases of the proposed mechanism that ultimately leads to vasodilation of feeding arterioles and increase in regional cerebral blood flow (VCCC: voltage–gated Ca²⁺ channel; Panx1: Pannexin 1 channel; P₂X: Ca²⁺–permeable ionotropic purinergic receptor; SK: small–conductance Ca²⁺–activated K⁺ channel; IK: intermediate–conductance Ca²⁺–activated K⁺ channel; Kir2.1: inward-rectifier K⁺ channel; ROS: reactive oxygen species).