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Non‐specificity of chloride channel blockers in rat cerebral arteries: block of the L‐type calcium channel
Author(s) -
Doughty Joanne M.,
Miller Alastair L.,
Langton Philip D.
Publication year - 1998
Publication title -
the journal of physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.802
H-Index - 240
eISSN - 1469-7793
pISSN - 0022-3751
DOI - 10.1111/j.1469-7793.1998.433bt.x
Subject(s) - channel blocker , chemistry , chloride channel , glibenclamide , constriction , patch clamp , niflumic acid , calcium channel , electrical impedance myography , calcium channel blocker , biophysics , calcium , medicine , endocrinology , biochemistry , receptor , vasodilation , organic chemistry , biology , diabetes mellitus
1 The effects of chloride channel blockers on pressure‐induced constriction, K + ‐induced force, and whole‐cell calcium channel currents were tested in rat cerebral arteries using isobaric and isometric myography, and patch clamp. 2 Under isobaric conditions at 75 mmHg, NPPB), a chloride channel blocker, reversibly depressed the myogenic constriction with an IC 50 of 32.8 ± 0.52 μ m (mean ± s.e.m., n = 5 ). Blockers of Ca 2+ ‐activated chloride channels, flufenamic acid (100 μ m ) and 9‐AC; 1 m m ), and the cystic fibrosis transmembrane conductance regulator (CFTR) Cl − channel blocker, glibenclamide (100 μ m ), were without effect in this tissue ( n = 3 ). 3 Under isobaric conditions at 20 mmHg, 37 °C, raising [K + ] o to 45 m m induced a constriction which was unaffected by 100 μ m NPPB ( n = 4 ). In contrast, at 75 mmHg and 18‐21 °C, 100 μ m NPPB completely and reversibly blocked a 45 m m K + ‐induced constriction ( n = 3 ). 4 Under isometric conditions, NPPB reversibly depressed a 45 m m K + ‐induced force with an IC 50 of 10.0 ± 0.76 μ m (mean ± s.e.m., n = 5 ). IAA‐94), another chloride channel blocker, depressed the K + ‐induced force with an IC 50 of 17.0 ± 1.2 μ m (mean ± s.e.m., n = 4 ). 5 Using whole‐cell patch clamp, 100 μ m NPPB or 200 μ m IAA‐94 blocked calcium channel currents carried by 10 m m Ba 2+ by 79.1 ± 1.7 and 39.8 ± 7.0 %, respectively (mean ± s.e.m., n = 6 ). 6 In summary, chloride channel blockers depress calcium channel currents in rat cerebral arteries, which could contribute to a reduction in myogenic contraction.