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Vascular Response in Mice Deficient in the Potassium Channel, TREK‐1
Author(s) -
Namiranian Khodadad,
Lloyd Eric E,
Marrelli Sean P,
Bryan Robert M
Publication year - 2009
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.23.1_supplement.613.27
Subject(s) - chemistry , potassium channel , cerebral arteries , vasodilation , endocrinology , medicine , knockout mouse , vascular smooth muscle , activator (genetics) , anatomy , biochemistry , smooth muscle , receptor , gene
TREK‐1, a member of the two‐pore domain potassium channel family, is highly expressed in the vascular system. We hypothesize that TREK‐1 is involved with regulating the diameter of cerebral vessels. A TREK‐1 knockout mouse (KO) was generated by replacing the first two coding exons of TREK‐1 with a neomycin/beta‐galactosidase cassette. KO mice had normal blood pressure and cardiac function. Vascular responses were measured in isolated basilar arteries (BA) and middle cerebral arteries (MCA). Linoleic acid (LA, 10 μM and 100 μM), an activator of TREK‐1 and Ca‐activated K channels (BK Ca ), dilated pre‐constricted BA of wild‐type (WT) and KO mice to a similar extent. However, after selectively blocking BK Ca with penitrem A, the dilation to LA in BA from KO mice was reduced 19±5% (n=6), while it was not affected in WT. This suggests that part of LA‐induced dilation is mediated via TREK‐1. Acetylcholine‐mediated dilations in BA and ATP‐mediated dilations in MCA of KO mice were not different from WT mice, either before or after inhibition of nitric oxide synthase. We conclude that TREK‐1 can regulate diameter of cerebral arteries; however, it does not appear to be involved with certain endothelial mediated dilations. This project is supported by a Predoctoral Fellowship 0815342F (KN) and grant 0665100Y (SPM) from American Heart Association, and NIH grants RO1 NS‐46666 (RMB), PO1 NS‐038660 (RMB), RO1 HL‐088435 (SPM).