Increased luminal pressure in brain capillaries drives TRPC3-dependent depolarization and constriction of transitional pericytes

• DOI: 10.1126/scisignal.ads1903
• Publication Date: 2025-04-29T17:58:11Z
• Authors: Hannah R. Ferris; Danielle A. Jeffrey; Mayra Bueno Guerrero; Lutz Birnbaumer; Fang Zheng; Fabrice Dabertrand
• Keywords: TRPC3; Pericyte; Mural cell; Myogenic contraction; Constriction

Cerebral autoregulation ensures constant blood flow, an essential condition of brain health. A fundamental parameter the circulation is dynamic regulation microvessel diameter to allow for adjustments in resistance pressure changes. Pericytes are a family mural cells that wrap around capillary endothelium and contribute control diameter. We sought determine whether how pericytes constrict response elevation with vivo two-photon microscopy, electrophysiology, ex arteriolar-capillary myography mice conditional cell knockout or expression genetically encoded Ca 2+ indicator. In first- fourth-order capillaries, displayed rapid measurable by decreasing luminal diameter, depolarizing membrane potentials, increasing cytoplasmic signaling. Pharmacological imaging approaches revealed transient receptor potential channel 3 (TRPC3) voltage-gated channels were sequentially activated promote fast constriction. Genetic ablation TRPC3 resulted decreased currents, loss depolarization, near-complete generation tone over standard curve transitional but not upstream arterioles. Together, our findings identify activation as critical proximal pericyte depolarization contraction pressure, highlighting signaling differences between arteriolar flow regulation.