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- Title
Astrocyte Contributions to Flow/Pressure-Evoked Parenchymal Arteriole Vasoconstriction.
- Authors
Ki Jung Kim; Iddings, Jennifer A.; Stern, Javier E.; Blanco, Víctor M.; Croom, Deborah; Kirov, Sergei A.; Filosa, Jessica A.
- Abstract
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 an in vitro rat/mouse brain slice model of perfused/pressurized PAs; studies were supplemented with in vivo astrocytic Ca2+ imaging. In vitro, astrocytes responded to PA flow/pressure increases with an increase in intracellular Ca2+. Astrocytic Ca2+ responses were corroborated in 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 inPAtone. Together our results support bidirectional signaling within the neurovascular unit and astrocytes as key modulators of PA tone.
- Subjects
EVOKED potentials (Electrophysiology); ASTROCYTES; VASOCONSTRICTION; CEREBRAL circulation; BASAL ganglia; ENDOTHELIAL cells
- Publication
Journal of Neuroscience, 2015, Vol 35, Issue 21, p8245
- ISSN
0270-6474
- Publication type
Article
- DOI
10.1523/JNEUROSCI.4486-14.2015