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(Circulation Research. 2001;88:849.)
© 2001 American Heart Association, Inc.

Editorial

K_ATP Channel Regulators

Balanced Diets Include Carbohydrates, Proteins, and Fats

Colin G. Nichols, Catherine A. Cukras

From the Department of Cell Biology and Physiology, Washington University School of Medicine, St Louis, Mo.

Correspondence to C.G. Nichols, Department of Cell Biology and Physiology, Washington University School of Medicine, 660 S Euclid Ave, St Louis, MO 63110. E-mail cnichols@cellbio.wustl.edu

Key Words: K_ATP • fatty acids • acyl–coenzyme A esters • ATP • PIP₂

	Introduction

 
In addition to the steep voltage-dependent K⁺ currents that play a role in repolarization of the heart, two major K⁺ conductances control the resting potential. The classical strong inward rectifier (I_K1) is constitutively active and acts to stabilize the resting potential. During depolarization, the strong rectification of I_K1 significantly reduces conductance, permitting a long action-potential plateau. The ATP-sensitive potassium current (I_K,ATP) is not usually active, but the density of underlying channels is so high that when activated in conditions of metabolic inhibition, such as ischemia, the action potential is massively shortened and the ventricle eventually becomes inexcitable. Although this channel was named for its defining property of inhibition by ATP, it is far from clear what signals actually lead to channel opening in physiological and pathophysiological conditions. A central paradox is the following: in excised membrane patches, K_ATP channels are half-maximally inhibited by 10 to 50 µmol/L ATP, but intracellular [ATP] does not fall below millimolar levels except under very extreme conditions.¹

It has long been recognized that MgADP and MgGDP act as antagonists to ATP inhibition of the channel,¹ and the cloning and expression of the relevant SUR and Kir6 subunits of the channel² have revealed details of this antagonism. ATP inhibition occurs through a direct interaction with the pore-forming Kir6 subunit; Mg-diphosphate activation of the channel occurs through interactions with the nucleotide-hydrolyzing domains of the SUR subunit (Figure). Both experiments and computer modeling indicate that the degree of activation of I_K,ATP conductance that . . . [Full Text of this Article]

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