Inhibition of the ATP-sensitive potassium channel from mouse pancreatic β-cells by surfactants

Abstract

1. 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.

2. All three detergents blocked K_ATP channel activity with the following order of potency: Tween 80 (K_i<∼83 nM)>Triton X100 (K_i=350 nM)>Cremophor. In all cases the block was poorly reversible.

3. Single-channel studies suggested that at low doses, the detergents act as slow blockers of the K_ATP channel.

4. Unlike the block produced by tolbutamide, that produced by detergent was not affected by intracellular Mg²⁺-nucleotide, diazoxide or trypsin treatment, nor did it involve an acceleration of rundown or increase in ATP sensitivity of the chanel.

5. The detergents could block the pore-forming subunit, Kir6.2ΔC26, which can be expressed independently of SUR₁ (the regulatory subunit of the K_ATP channel). These data suggest that the detergents act on Kir6.2 and not SUR₁.

6. The detergents had no effect on another member of the inward rectifier family: Kir1.1a (ROMK1).

7. 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.

8. Like other insulin secretagogues that act by blocking the K_ATP channel, Cremophor elevated intracellular Ca²⁺ in single β-cells to levels that would be expected to elicit insulin secretion.

9. 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

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