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The effects of cromakalim on ATP‐sensitive potassium channels in insulin‐secreting cells
Author(s) -
Dunne M.J.,
Aspinall R.J.,
Petersen O.H.
Publication year - 1990
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.1476-5381.1990.tb14672.x
Subject(s) - cromakalim , diazoxide , potassium channel , potassium channel opener , glibenclamide , chemistry , adenosine triphosphate , medicine , biophysics , endocrinology , biochemistry , insulin , biology , diabetes mellitus
1 The single‐channel current recording technique has been used to investigate the effects of cromakalim, diazoxide and ATP, separately and combined, on the opening of ATP‐sensitive potassium channels in the insulin‐secreting cell‐line RINm5F. The actions of these drugs have been studied using the permeabilized open‐cell variation of the patch‐clamp technique. 2 In the absence of internal ATP, cromakalim (80–200 μ m ) was unable to open ATP‐sensitive K + channels but when ATP was present both cromakalim and diazoxide caused channel openings. 3 Interactions between ATP and cromakalim seemed competitive. Concentrations of cromakalim in the range 80–200 μ m readily activated channels inhibited by 0.1 m m ATP, but had no effects when the concentration of ATP was increased to 0.5–2 m m . Only when the concentration of cromakalim was increased to 400–800 μ m could opening of 0.5–2 m m ATP‐inhibited channels be regularly observed. In the continued presence of cromakalim (400–800 μ m ), an increase in the internal concentration of ATP from either 0.25 to 0.5 m m or 1 to 2 m m , inhibited cromakalim‐activated K + channels. 4 Activation of ATP‐inhibited K + channels was abolished by replacing ATP with ATPγS and cromakalim had no effects on ATPγS‐inhibited channels. This suggests that cromakalim may open K ATP channels in insulin‐secreting cells by a mechanism which involves protein phosphorylation.