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Mechanism of action of a K+ channel activator BRL 38227 on ATP‐sensitive K+ channels in mouse skeletal muscle fibres.
Author(s) -
Hussain M,
Wareham A C,
Head S I
Publication year - 1994
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 - 10.1113/jphysiol.1994.sp020271
Subject(s) - chemistry , glibenclamide , potassium channel , cromakalim , mechanism of action , biophysics , activator (genetics) , atp sensitive potassium channel , muscle contraction , medicine , biochemistry , pharmacology , endocrinology , stereochemistry , biology , agonist , receptor , in vitro , diabetes mellitus
1. Investigations were made into the effects of BRL 38227, a potassium channel activator, on ATP‐sensitive potassium channels (K+ATP channels) in single fibres dissociated from the flexor digitorum brevis muscle of C57BL/6J mice. 2. In cell‐attached patches BRL 38227 (100 microM) caused activation of a glibenclamide‐sensitive potassium current. Linear slope conductance of the inward current, partial rectification of the outward current and glibenclamide sensitivity indicate that K+ATP channels are the site of action of BRL 38227. 3. In the absence of ATP at the cytoplasmic side of excised inside‐out patches, BRL 38227 caused direct and magnesium‐dependent activation of K+ATP channels. The degree of activation diminished with successive applications of BRL 38227. 4. BRL 38227 also caused activation of K+ATP channels in the presence of low (< 100 microM) but not high (1.0 mM) ATP, particularly in patches containing large numbers of channels. 5. BRL 38227 and 5 microM MgATP failed to activate channels following complete run‐down. 6. Results show that BRL 38227 caused direct activation of K+ATP in skeletal muscle and that this was mediated through a magnesium‐dependent binding site rather than alleviation of inhibition by competitive displacement of ATP from the inhibitory site.