Merck

Brain endothelial cell TRPA1 channels initiate neurovascular coupling.

eLife (2021-02-27)
Pratish Thakore, Michael G Alvarado, Sher Ali, Amreen Mughal, Paulo W Pires, Evan Yamasaki, Harry At Pritchard, Brant E Isakson, Cam Ha T Tran, Scott Earley
ABSTRACT

Cerebral blood flow is dynamically regulated by neurovascular coupling to meet the dynamic metabolic demands of the brain. We hypothesized that TRPA1 channels in capillary endothelial cells are stimulated by neuronal activity and instigate a propagating retrograde signal that dilates upstream parenchymal arterioles to initiate functional hyperemia. We find that activation of TRPA1 in capillary beds and post-arteriole transitional segments with mural cell coverage initiates retrograde signals that dilate upstream arterioles. These signals exhibit a unique mode of biphasic propagation. Slow, short-range intercellular Ca2+ signals in the capillary network are converted to rapid electrical signals in transitional segments that propagate to and dilate upstream arterioles. We further demonstrate that TRPA1 is necessary for functional hyperemia and neurovascular coupling within the somatosensory cortex of mice in vivo. These data establish endothelial cell TRPA1 channels as neuronal activity sensors that initiate microvascular vasodilatory responses to redirect blood to regions of metabolic demand.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
Triton X-100, laboratory grade
Sigma-Aldrich
泰莫西芬, ≥99%
Sigma-Aldrich
腺苷 5'-三磷酸 二钠盐 水合物, Grade I, ≥99%, from microbial
Sigma-Aldrich
Nω-硝基-L-精氨酸甲酯 盐酸盐, ≥98% (TLC), powder
Sigma-Aldrich
吲哚美辛, 98.5-100.5% (in accordance with EP)
Sigma-Aldrich
抗-肌动蛋白, α-平滑肌- Cy3抗体,小鼠单克隆, clone 1A4, purified from hybridoma cell culture
Sigma-Aldrich
三磷酸腺苷双磷酸酶 来源于马铃薯, ATPase ≥200 units/mg protein, lyophilized powder