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Differential roles for IKCa and SKCa channels in EDHF‐type responses in mouse mesenteric arteries
Author(s) -
Gallagher Nicola Tracy,
Garland Chris,
Dora Kim
Publication year - 2006
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.20.4.a272-b
Subject(s) - apamin , mesenteric arteries , hyperpolarization (physics) , phenylephrine , iberiotoxin , medicine , biophysics , endocrinology , membrane potential , contraction (grammar) , chemistry , anatomy , vasodilation , artery , potassium channel , biology , stereochemistry , nuclear magnetic resonance spectroscopy , blood pressure
Activation of intermediate‐ and small‐conductance Ca 2+ ‐activated K + channels (IK Ca and SK Ca ) by the endothelium‐dependent agonist SLIGRL, evokes smooth muscle cell hyperpolarization and relaxation in mouse mesenteric arteries. The aim of this study was to establish whether differential activation of the K Ca channels occurred in the presence and absence of pre‐contraction. Isolated mesenteric arteries were mounted isometrically, enabling simultaneous recording of smooth muscle cell membrane potential and tension. In the presence of the NO‐synthase inhibitor L ‐NAME (100 μM), SLIGRL (1–30μM) evoked both relaxation and hyperpolarization. In un‐stimulated arteries the maximal increase in membrane potential (18.1 ± 1.0 mV, n = 14) was almost fully blocked by the selective inhibitor of IK Ca , TRAM‐34 (1μM) alone. However, when arteries were pre‐contracted and depolarized with phenylephrine (0.2–3μM), similar levels of inhibition were achieved only in the presence of both TRAM‐34 (1μM) and the selective SK Ca inhibitor, apamin (50nM). These data suggest that IK Ca are the predominant endothelial channels associated with SLIGRL‐induced smooth muscle hyperpolarization in mouse mesenteric arteries, whilst SK Ca contribute to SLIGRL‐evoked repolarization and relaxation subsequent to depolarization. These findings are in direct contrast to those obtained in the rat mesenteric artery, and appear to reflect the sub‐cellular profile of K Ca channel expression. These data reiterate the importance of using selective inhibitors at different levels of pre‐contraction when studying EDHF responses. Supported by the Wellcome Trust