ATP Sensitivity of the ATP-Sensitive K + Channel in Intact and Permeabilized Pancreatic β-Cells
Andrei I. Tarasov ,
Christophe A.J. Girard and
Frances M. Ashcroft
From the University Laboratory of Physiology, Oxford University, Oxford, U.K
Address correspondence and reprint requests to Prof. F.M. Ashcroft, University Laboratory of Physiology, Parks Road, Oxford,
OX1 3PT, U.K. E-mail: frances.ashcroft{at}physiol.ox.ac.uk
Abstract
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 K ATP channel activity, and the channel sensitivity to inhibition by ATP in its native environment, remain controversial. Here,
we used α-toxin to permeabilize single pancreatic β-cells and measure K ATP 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 K ATP channel activity in intact cells. Thus, our results show that the principal metabolic regulators of K ATP channel activity are MgATP and MgADP.
[ATP]i, intracellular concentration of ATP
[ATP]sm, submembrane ATP concentration
KATP channel, ATP-sensitive K+ channel
LC-CoA, long-chain acyl-CoA
NBD, nucleotide-binding domain
PIP2, phosphatidylinositol 4,5-bisphosphate
SUR, sulfonylurea receptor
Footnotes
Additional information for this article can be found in an online appendix at http://diabetes.diabetesjournals.org .
The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore
be hereby marked “advertisement” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
Accepted June 5, 2006.
Received March 19, 2006.
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ATP Sensitivity of the ATP-Sensitive K+ Channel in Intact and Permeabilized Pancreatic β-Cells

10.2337/db06-0360