RT Journal Article
T1 Adenosine signaling activates ATP-sensitive K channels in endothelial cells and pericytes in CNS capillaries.
A1 Sancho González, María
A1 Klug, Nicholas R
A1 Mughal, Amreen
A1 Koide, Masayo
A1 Huerta de la Cruz, Saul
A1 Heppner, Thomas J
A1 Bonev, Adrian D
A1 Hill-Eubanks, David
A1 Nelson, Mark T
AB The dense network of capillaries composed of capillary endothelial cells (cECs) and pericytes lies in close proximity to all neurons, ideally positioning it to sense neuron- and glial-derived compounds that enhance regional and global cerebral perfusion. The membrane potential () of vascular cells serves as the physiological bridge that translates brain activity into vascular function. In other beds, the ATP-sensitive K (K) channel regulates in vascular smooth muscle, which is absent in the capillary network. Here, with transgenic mice that expressed a dominant-negative mutant of the pore-forming Kir6.1 subunit specifically in brain cECs or pericytes, we demonstrated that K channels were present in both cell types and robustly controlled . We further showed that the signaling nucleotide adenosine acted through A receptors and the Gα/cAMP/PKA pathway to activate capillary K channels. Moreover, K channel stimulation in vivo increased cerebral blood flow (CBF), an effect that was blunted by expression of the dominant-negative Kir6.1 mutant in either capillary cell type. These findings establish an important role for K channels in cECs and pericytes in the regulation of CBF.
PB Science
SN 1937-9145
YR 2022
FD 2022
LK https://hdl.handle.net/20.500.14352/134675
UL https://hdl.handle.net/20.500.14352/134675
LA eng
NO Sancho M, Klug NR, Mughal A, Koide M, Huerta de la Cruz S, Heppner TJ, Bonev AD, Hill-Eubanks D, Nelson MT. Adenosine signaling activates ATP-sensitive K+ channels in endothelial cells and pericytes in CNS capillaries. Sci Signal. 2022 Mar 29;15(727):eabl5405. doi: 10.1126/scisignal.abl5405.
NO National Heart, Lung, andBlood Institute of NIH (F32HL152576 to N.R.K. and P20GM135007 to M.K.) and the AmericanHeart Association (20POST35210155 and Career Development Award 856791 to A.M.).Support was also provided by the Million Dollar Bike Ride Grant Program (MDBR-21-101-CADASIL to M.K.), the Totman Medical Research Trust (to M.T.N.), and the European UnionHorizon 2020 Research and Innovation Programme (grant agreement 666881, SVDs@target, toM.T.N.), as well as grants from the National Institute of Neurological Disorders and Stroke(NINDS) and National Institute on Aging (NIA) (R01-NS-110656 to M.T.N.), the National Instituteof General Medical Sciences (NIGMS) (P20-GM-135007 to M.T.N.), and the National Heart, Lung,and Blood Institute (NHLBI) of NIH (R35-HL-140027 to M.T.N.)
DS Docta Complutense
RD 30 abr 2026