TY - JOUR
T1 - Astrocyte contributions to flow/pressure-evoked parenchymal arteriole vasoconstriction
AU - Kim, Ki Jung
AU - Iddings, Jennifer A.
AU - Stern, Javier Eduardo
AU - Blanco, Víctor M.
AU - Croom, Deborah
AU - Kirov, Sergei A
AU - Filosa, Jessica Andrea
N1 - Publisher Copyright:
© 2015 the authors.
PY - 2015/5/27
Y1 - 2015/5/27
N2 - 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 Ca 2+ dynamics were measured using an in vitro rat/mouse brain slice model of perfused/pressurized PAs; studies were supplemented with in vivo astrocytic Ca 2+ imaging. In vitro, astrocytes responded to PA flow/pressure increases with an increase in intracellular Ca 2+. Astrocytic Ca 2+ responses were corroborated in vivo, where acute systemic phenylephrine-induced increases in blood pressure evoked a significant increase in astrocytic Ca 2+. In vitro, flow/pressure-evoked vasoconstriction was blunted when the astrocytic syncytium was loaded with BAPTA (chelating intracellular Ca 2+) and enhanced when high Ca 2+ 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.
AB - 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 Ca 2+ dynamics were measured using an in vitro rat/mouse brain slice model of perfused/pressurized PAs; studies were supplemented with in vivo astrocytic Ca 2+ imaging. In vitro, astrocytes responded to PA flow/pressure increases with an increase in intracellular Ca 2+. Astrocytic Ca 2+ responses were corroborated in vivo, where acute systemic phenylephrine-induced increases in blood pressure evoked a significant increase in astrocytic Ca 2+. In vitro, flow/pressure-evoked vasoconstriction was blunted when the astrocytic syncytium was loaded with BAPTA (chelating intracellular Ca 2+) and enhanced when high Ca 2+ 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.
KW - Astrocyte
KW - Calcium
KW - Myogenic
KW - Neurovascular
KW - Parenchymal arteriole
KW - Vascular tone
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UR - http://www.scopus.com/inward/citedby.url?scp=84930255307&partnerID=8YFLogxK
U2 - 10.1523/JNEUROSCI.4486-14.2015
DO - 10.1523/JNEUROSCI.4486-14.2015
M3 - Article
C2 - 26019339
AN - SCOPUS:84930255307
SN - 0270-6474
VL - 35
SP - 8245
EP - 8257
JO - Journal of Neuroscience
JF - Journal of Neuroscience
IS - 21
ER -