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Inhibition of the ATP‐sensitive potassium channel from mouse pancreatic β ‐cells by surfactants
Author(s) -
Smith Paul A,
Proks Peter
Publication year - 1998
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 - 10.1038/sj.bjp.0701858
Subject(s) - diazoxide , potassium channel , chemistry , tolbutamide , intracellular , patch clamp , biophysics , biochemistry , channel blocker , potency , inward rectifier potassium ion channel , kir6.2 , protein subunit , endocrinology , insulin , biology , ion channel , in vitro , calcium , organic chemistry , receptor , gene
We have used patch‐clamp methods to study the effects of the detergents, Cremophor, Tween 80 and Triton X100 on the K ATP channel in the pancreatic β‐cell from mouse. All three detergents blocked K ATP channel activity with the following order of potency: Tween 80 ( K i <∼83 n M )>Triton X100 ( K i =350 n M )>Cremophor. In all cases the block was poorly reversible. Single‐channel studies suggested that at low doses, the detergents act as slow blockers of the K ATP channel. Unlike the block produced by tolbutamide, that produced by detergent was not affected by intracellular Mg 2+ ‐nucleotide, diazoxide or trypsin treatment, nor did it involve an acceleration of rundown or increase in ATP sensitivity of the chanel. The detergents could block the pore‐forming subunit, Kir6.2ΔC26, which can be expressed independently of SUR 1 (the regulatory subunit of the K ATP channel). These data suggest that the detergents act on Kir6.2 and not SUR 1 . The detergents had no effect on another member of the inward rectifier family: Kir1.1a (ROMK1). Voltage‐dependent K‐currents in the β‐cell were reversibly blocked by the detergents with a far lower potency than that found for the K ATP channel. Like other insulin secretagogues that act by blocking the K ATP channel, Cremophor elevated intracellular Ca 2+ in single β‐cells to levels that would be expected to elicit insulin secretion. Given the role of the K ATP channel in many physiological processes, we conclude that plasma borne detergent may have pharmacological actions mediated through blockage of the K ATP channel