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Amantadine and sparteine inhibit ATP‐regulated K‐currents in the insulin‐secreting β‐cell line, HIT‐T15
Author(s) -
Ashcroft Frances M.,
Kerr Amanda J.,
Gibson John S.,
Williams Beatrice A.
Publication year - 1991
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.1991.tb12472.x
Subject(s) - sparteine , amantadine , patch clamp , biophysics , chemistry , potassium channel , insulin , membrane potential , pharmacology , stereochemistry , biochemistry , endocrinology , biology , receptor
1 The effects of pharmacological agents that potentiate insulin release were studied on ATP‐regulated K‐currents (K‐ATP currents) in the insulin‐secreting β‐cell line HIT‐T15 by use of patch‐clamp methods. 2 The tricyclic drug, 1‐adamantanamine (amantadine), reversibly inhibited both whole‐cell currents (with a K i of 120 μ m ) and single channel currents in inside‐out patches. This effect was principally due to an increase in a long closed state which reduced the channel open probability. The related compound, 1‐adamantanol, in which the amino group is substituted by a hydroxyl one, did not inhibit K‐ATP currents substantially. 3 The alkaloid, sparteine, reversibly inhibited both whole‐cell K‐ATP currents ( K i = 171 μ m ) and single channel currents in inside‐out patches. 4 The results suggest that sparteine and amantadine can block the K‐ATP channel from either side of the membrane and support the idea that at least part of the stimulatory effect of these agents on insulin secretion results from inhibition of this channel.