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Inhibition of the ATP‐sensitive potassium channel by class I antiarrhythmic agent, cibenzoline, in rat pancreatic β‐cells

1993; Wiley; Volume: 109; Issue: 4 Linguagem: Inglês

10.1111/j.1476-5381.1993.tb13753.x

1476-5381

Masafumi Kakei, Mitsuhiro Nakazaki, Takeshi Kamisaki, Issei Nagayama, Yuzo Fukamachi, Hiromitsu Tanaka,

Cannabis and Cannabinoid Research

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. 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. 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. 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 . Cibenzoline blocked substantially the ATP‐sensitive K + channel current when applied at the inner side of the membrane in isolated inside‐out membrane patches. 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.