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Inhibition of the ATP‐sensitive potassium channel by class I antiarrhythmic agent, cibenzoline, in rat pancreatic β‐cells
Author(s) -
Kakei Masafumi,
Nakazaki Mitsuhiro,
Kamisaki Takeshi,
Nagayama Issei,
Fukamachi Yuzo,
Tanaka Hiromitsu
Publication year - 1993
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.1476-5381.1993.tb13753.x
Subject(s) - pipette , patch clamp , biophysics , potassium channel , membrane potential , chemistry , medicine , endocrinology , electrophysiology , biology
1 Cibenzoline, a class I antiarrhythmic agent, was investigated for its effect on the ATP‐sensitive K + channel of pancreatic β‐cells by the patch clamp technique. 2 In perforated patch clamp experiments, cibenzoline depolarized the membrane of single β‐cells and thereafter, caused firing of action potentials in the presence of 2.8 m m glucose. 3 Cibenzoline inhibited the activity of the ATP‐sensitive K + channel in cell‐attached recordings in the presence of 2.8 m m glucose and evoked repetitive fluctuations of the baseline current, apparently reflecting the action potentials of the β‐cell. 4 In whole‐cell clamp experiments, time‐independent outward current was induced by depleting cytoplasmic ATP with 0.1 m m ATP and 0.1 m m ADP in the solution contained in the pipette. The outward current was inhibited by cibenzoline in a dose‐dependent manner in the concentration range of 1 μ m to 100 μ m and half maximum inhibition occurred at 1.5 μ m . 5 Cibenzoline blocked substantially the ATP‐sensitive K + channel current when applied at the inner side of the membrane in isolated inside‐out membrane patches. 6 It is concluded that cibenzoline blocks the ATP‐sensitive K + channel of pancreatic β‐cells and, thereby, stimulates insulin secretion at sub‐stimulatory levels of glucose.