Astrocyte contributions to flow/pressure-evoked parenchymal arteriole vasoconstriction
| Autor: | Ki Jung Kim, Víctor M. Blanco, Jennifer A. Iddings, Javier E. Stern, Deborah Croom, Jessica A. Filosa, Sergei A. Kirov |
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| Rok vydání: | 2015 |
| Předmět: |
TRPV4
Male TRPV Cation Channels Mice Transgenic Biology Cerebral autoregulation chemistry.chemical_compound Mice Slice preparation Organ Culture Techniques BAPTA Arteriole medicine.artery medicine Animals Homeostasis Rats Wistar General Neuroscience Purinergic receptor Brain Articles Rats Mice Inbred C57BL Arterioles medicine.anatomical_structure chemistry Vasoconstriction Anesthesia Astrocytes Cerebrovascular Circulation Biophysics medicine.symptom Astrocyte |
| Zdroj: | The Journal of neuroscience : the official journal of the Society for Neuroscience. 35(21) |
| ISSN: | 1529-2401 |
| Popis: | Basal and activity-dependent cerebral blood flow changes are coordinated by the action of critical processes, including cerebral autoregulation, endothelial-mediated signaling, and neurovascular coupling. The goal of our study was to determine whether astrocytes contribute to the regulation of parenchymal arteriole (PA) tone in response to hemodynamic stimuli (pressure/flow). Cortical PA vascular responses and astrocytic Ca2+dynamics were measured using anin vitrorat/mouse brain slice model of perfused/pressurized PAs; studies were supplemented within vivoastrocytic Ca2+imaging.In vitro, astrocytes responded to PA flow/pressure increases with an increase in intracellular Ca2+. Astrocytic Ca2+responses were corroboratedin vivo, where acute systemic phenylephrine-induced increases in blood pressure evoked a significant increase in astrocytic Ca2+.In vitro, flow/pressure-evoked vasoconstriction was blunted when the astrocytic syncytium was loaded with BAPTA (chelating intracellular Ca2+) and enhanced when high Ca2+or ATP were introduced to the astrocytic syncytium. Bath application of either the TRPV4 channel blocker HC067047 or purinergic receptor antagonist suramin blunted flow/pressure-evoked vasoconstriction, whereas K+and 20-HETE signaling blockade showed no effect. Importantly, we found TRPV4 channel expression to be restricted to astrocytes and not the endothelium of PA. We present evidence for a novel role of astrocytes in PA flow/pressure-evoked vasoconstriction. Our data suggest that astrocytic TRPV4 channels are key molecular sensors of hemodynamic stimuli and that a purinergic, glial-derived signal contributes to flow/pressure-induced adjustments in PA tone. Together our results support bidirectional signaling within the neurovascular unit and astrocytes as key modulators of PA tone. |
| Databáze: | OpenAIRE |
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