AJP - Cell Physiology The American Physiological Society Ībstract Membrane-bound anionic phospholipids such as phosphatidylinositols have the capacity to modulate ATP-sensitive potassium (K ATP ) channels through a mechanism involving long-range electrostatic interaction between the lipid headgroup and channel. First published Septem10.1152/ajpcell.00255.2002 Copyright © 2003 the American Physiological Society Section 1734 solely to indicate this fact. The article must therefore be hereby marked “ advertisement ” in accordance with 18 U.S.C. The costs of publication of this article were defrayed in part by the payment of page charges. of Tennessee Health Science Center, College of Medicine, Memphis, Tennessee 38163 (E-mail: ). Address for reprint requests and other correspondence: Z.

adenosine 5′-triphosphate-sensitive potassium channel phosphatidic acid sulfonylurea Footnotes This work was supported by National Institutes of Health Grants HL-58133 and GM-61943 and a Grant-in-Aid from the American Heart Association Southeast Affiliation. Results indicate that multiple effects of anionic phospholipids on K ATP channels are related phenomena and can likely be attributed to a common mechanism, but additional specific effects due to other mechanisms may also coincide. This impact on gating kinetics clearly distinguishes PA's effects from those of phosphatidylinositols. These effects match the spectrum of phosphatidylinositols' effects, but, in addition, PA also induced a novel pattern in gating kinetics, represented by a decreased mean open time (from 12.2 ± 2.0 to 3.3 ± 0.7 ms). Channels treated with PA (0.2–1 mg/ml applied to the cytoplasmic side of the membrane) exhibited higher activity, lower sensitivity to ATP inhibition, less Mg 2+ -dependent nucleotide stimulation, and poor sulfonylurea inhibition. The present study investigated whether phosphatidic acid (PA), an anionic phospholipid substantially different in structure from phosphatidylinositols, evokes effects similar to phosphatidylinositols on native K ATP channels of rat heart and heterogeneous Kir6.2/SUR2A channels. However, it has not yet been determined whether the multiple effects of phosphatidylinositols reported in the literature all result from this general electrostatic interaction or require a specific headgroup structure. Phosphatidic acid stimulates cardiac KATPchannels like phosphatidylinositols, but with novel gating kinetics Phosphatidic acid stimulates cardiac KATPchannels like phosphatidylinositols, but with novel.Ībstract Membrane-bound anionic phospholipids such as phosphatidylinositols have the capacity to modulate ATP-sensitive potassium (K ATP ) channels through a mechanism involving long-range electrostatic interaction between the lipid headgroup and channel.

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