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Effect of focal cerebral ischemia on BK Ca and TRPV4 in rat middle cerebral artery
Author(s) -
Murphy Timothy V,
Nguyen Hong L,
Grayson T Hilton,
Jones Nicole M,
Sandow Shaun L
Publication year - 2016
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.30.1_supplement.1275.6
Subject(s) - iberiotoxin , cerebral arteries , middle cerebral artery , trpv4 , vascular smooth muscle , medicine , endocrinology , stroke (engine) , ischemia , chemistry , anatomy , anesthesia , vasodilation , transient receptor potential channel , receptor , smooth muscle , engineering , mechanical engineering
Large‐conductance Ca 2+ ‐sensitive K + channels (BK Ca ) are prime regulators of vascular smooth muscle cell membrane potential and contraction and may be coupled to transient receptor potential vanillioid‐4 (TRPV4) channels. This study examined the expression and function of BK Ca and TRPV4 in rat middle‐cerebral arteries (MCA) in stroke. Male Sprague‐Dawley rats were subject to focal cerebral ischemic stroke by localized bolus injection of endothelin‐1 (120 pmol). Controls received saline (0.9%). Five days later, animals were euthanized and the MCAs removed. Immunofluorescence studies showed increased BK Ca expression (α‐ and β 1 ‐subunits) in the smooth muscle cells of the arteries from rats with stroke. BK Ca was also expressed in the endothelium of MCA from stroke rats, in contrast with arteries from controls. TRPV4 was expressed in both endothelial and smooth muscle cells of the MCA, and expression in both cell types was increased in arteries from stroke rats. Pressurized (80 mmHg) arteries developed myogenic tone, the degree of myogenic tone was not different between arteries from control and stroke rats. The BK Ca blocker iberiotoxin (0.1 μM) constricted arteries from stroke rats to greater extent than control MCA. The TRPV4 activator GSK1016790A (GSK) caused concentration‐dependent dilation of MCAs from control and stroke rats; there was no effect of stroke on responses to GSK. In both control and stroke rats, MCA dilation induced by GSK was inhibited by the TRPV4 blocker HC‐067047 (0.3 μM) but not by iberiotoxin. These studies suggest increased BK Ca expression and activity contribute to modulation of MCA tone post‐stroke. TRPV4 do not induce dilation of rat MCA through activation of BK Ca . Support or Funding Information This work was supported by the Brain Foundation.