title: Activation of TRPV4 channels does not mediate inversion of neurovascular coupling after SAH.
abstract: Neurovascular coupling (NVC) allows increased blood flow to metabolically active neurons and involves the Ca²⁺ -dependent release of vasodilator influences by astrocyte endfeet that encase parenchymal arterioles. We previously reported inversion of NVC from dilation to constriction in brain slices from subarachnoid hemorrhage (SAH) model rats. Corresponding to NVC inversion, there was a marked increase in the amplitude of spontaneous Ca²⁺ oscillations in astrocyte endfeet. Calcium-permeable transient receptor potential vanilloid (TRPV)-4 channels have been reported in astrocyte endfeet, and activators of these channels enhance Ca²⁺ oscillations in healthy animals. Here, we examined the role of TRPV4 channels in the development of high-amplitude spontaneous Ca²⁺ oscillations in astrocyte endfeet and the inversion of neurovascular coupling after SAH. Treatment of brain slices with the TRPV4 channel antagonist, HC-067047 (10 μM), did not alter the amplitude of spontaneous Ca²⁺ oscillations after SAH. In addition, HC-067047 did not inhibit or change SAH-induced inversion of neurovascular coupling. In summary, TRPV4 channels do not appear to be involved in the inversion of neurovascular coupling after SAH. Further studies examining the impact of SAH on additional Ca²⁺ signaling pathways in astrocytes are likely to reveal valuable insights into new therapeutic strategies to advance SAH treatments.
authors.affiliation: Department of Pharmacology, University of Vermont College of Medicine, 89 Beaumont Avenue, Burlington, VT, USA, masayo.koide@uvm.edu.
authors.forename: Masayo
authors.initials: M
authors.lastname: Koide
authors.forename: George C
authors.initials: GC
authors.lastname: Wellman
mesh_terms: D000818:Animals; D001253:Astrocytes / Q000187:drug effects / Q000502:physiology*; D020013:Calcium Signaling / Q000187:drug effects / Q000502:physiology*; D004195:Disease Models, Animal; D006940:Hyperemia / Q000188:drug therapy / Q000503:physiopathology; D008297:Male; D009025:Morpholines / Q000494:pharmacology*; D009924:Organ Culture Techniques; D011758:Pyrroles / Q000494:pharmacology*; D017207:Rats, Sprague-Dawley; D013345:Subarachnoid Hemorrhage / Q000188:drug therapy / Q000503:physiopathology*; D050916:TRPV Cation Channels / Q000037:antagonists & inhibitors / Q000502:physiology*
chemical_list: C573308:HC-067047; D009025:Morpholines; D011758:Pyrroles; D050916:TRPV Cation Channels; C486577:Trpv4 protein, rat