Klug, Nicholas RSancho González, MaríaGonzales, Albert LHeppner, Thomas JO'Brien, Rochelle Irene CHill-Eubanks, DavidNelson, Mark T2026-04-132026-04-132023Klug NR, Sancho M, Gonzales AL, Heppner TJ, O'Brien RIC, Hill-Eubanks D, Nelson MT. Intraluminal pressure elevates intracellular calcium and contracts CNS pericytes: Role of voltage-dependent calcium channels. Proc Natl Acad Sci U S A. 2023 Feb 28;120(9):e2216421120. doi: 10.1073/pnas.2216421120.1091-649010.1073/pnas.2216421120https://hdl.handle.net/20.500.14352/134683Arteriolar smooth muscle cells (SMCs) and capillary pericytes dynamically regulate blood flow in the central nervous system in the face of fluctuating perfusion pressures. Pressure-induced depolarization and Ca elevation provide a mechanism for regulation of SMC contraction, but whether pericytes participate in pressure-induced changes in blood flow remains unknown. Here, utilizing a pressurized whole-retina preparation, we found that increases in intraluminal pressure in the physiological range induce contraction of both dynamically contractile pericytes in the arteriole-proximate transition zone and distal pericytes of the capillary bed. We found that the contractile response to pressure elevation was slower in distal pericytes than in transition zone pericytes and arteriolar SMCs. Pressure-evoked elevation of cytosolic Ca and contractile responses in SMCs were dependent on voltage-dependent Ca channel (VDCC) activity. In contrast, Ca elevation and contractile responses were partially dependent on VDCC activity in transition zone pericytes and independent of VDCC activity in distal pericytes. In both transition zone and distal pericytes, membrane potential at low inlet pressure (20 mmHg) was approximately -40 mV and was depolarized to approximately -30 mV by an increase in pressure to 80 mmHg. The magnitude of whole-cell VDCC currents in freshly isolated pericytes was approximately half that measured in isolated SMCs. Collectively, these results indicate a loss of VDCC involvement in pressure-induced constriction along the arteriole-capillary continuum. They further suggest that alternative mechanisms and kinetics of Ca elevation, contractility, and blood flow regulation exist in central nervous system capillary networks, distinguishing them from neighboring arterioles.engjournal articlehttps://doi.org/10.1073/pnas.221642112036802432https://www.pnas.org/open access612Pericytes; vascular tone; cerebral blood flow; autoregulation.Ciencias Biomédicas24 Ciencias de la Vida