期刊
DIABETES
卷 55, 期 9, 页码 2446-2454出版社
AMER DIABETES ASSOC
DOI: 10.2337/db06-0360
关键词
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资金
- Wellcome Trust Funding Source: Medline
ATP-sensitive K(+) channels (K(ATP) channels) couple cell metabolism to electrical activity and thereby to physiological processes such as hormone secretion, muscle contraction, and neuronal activity. However, the mechanism by which metabolism regulates KATP channel activity, and the channel sensitivity to inhibition by ATP in its native environment, remain controversial. Here, we used a-toxin to permeabilize single pancreatic beta-cells and measure KATP channel ATP sensitivity. We show that the channel ATP sensitivity is approximately sevenfold lower in the permeabilized cell than in the inside-out patch and that this is caused by interaction of Mg-nucleotides with the nucleotide-binding domains of the SUR1 subunit of the channel. The ATP sensitivity observed in permeabilized cells accounts quantitatively for KATp channel activity in intact cells. Thus, our results show that the principal metabolic regulators of KATp channel activity are MgATP and MgADP.
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