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Dual effects of diazoxide on ATP‐K + currents recorded from an insulin‐secreting cell line
Author(s) -
Kozlowski R.Z.,
Hales C.N.,
Ashford M.L.J.
Publication year - 1989
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.1476-5381.1989.tb12560.x
Subject(s) - diazoxide , biophysics , cromakalim , membrane potential , patch clamp , chemistry , intracellular , adenosine triphosphate , potassium channel , endocrinology , medicine , biochemistry , glibenclamide , biology , insulin , diabetes mellitus , receptor
1 The effects of diazoxide on ATP‐K + channel currents, recorded from the insulin‐secreting cell line, CRI‐G1, were studied using patch‐clamp techniques. 2 Under current‐clamp recording conditions diazoxide (0.6 m m ), inhibited action potential activity and hyperpolarized CRI‐G1 cells with a concomitant increase in membrane conductance. Recordings from voltage‐clamped whole‐cells and isolated patches indicate that activation of ATP‐K + channel currents underlie these effects. 3 Diazoxide elicited an activation of ATP‐K + channels which had been partially inhibited by ATP, on application to either surface of the plasma membrane, although it was more effective when applied directly to the cytoplasmic side. Activation of the ATP‐K + currents involves an increase in the single channel open‐state probability and an apparent increase in the number of functional channels. 4 Activation was observed only when Mg‐ATP was present in the cytoplasmic bathing solution. There was no activation of currents by diazoxide when ATP, in the absence of Mg 2+ ions, or Mg‐AMP‐PNP was present to inhibit the ATP‐K + channels. 5 In the absence of ATP and Mg 2+ ions in the cytoplasmic bathing solution, diazoxide (0.6 m m ) produced an inhibition of ATP‐K + currents. 6 Cromakalim (BRL 34915) at 10 μ m and 100 μ m had no significant effects on ATP‐K + currents. 7 It is concluded that diazoxide‐induced activation of ATP‐K + channel currents probably involves phosphorylation of the channel or some closely associated membrane protein.