Abstract
The inside-out configuration of the patch-clamp technique was used to study the effect of glibenclamide on the ATP-sensitive K+ channel current in isolated guinea-pig ventricular myocytes. The inhibitory effect of glibenclamide was tested in the bath solution containing two different concentrations of ATP (100 μM and 200 μM). It was found that the effect of the drug on the KATP current was stronger in the presence of the higher concentration of ATP. The blocking effect of glibenclamide on the channels was weaker if, in addition to ATP, ADP was applied in the intracellular solution. Similarly, the inhibitory effect of the drug was not pronounced for the channels reactivated by ADP after run-down. As application of the drug in the presence and absence of Mg2+ did not show different effects on the channel inhibition, we concluded that the effect of glibenclamide may not depend on the phosphorylation of the channel protein. These results suggest that in addition of the previously described effect of ADP, ATP also has some modulatory effect on inhibition of the KATP channel by glibenclamide.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Noma A: ATP-regulated K+ channels in cardiac muscle. Nature 305: 147–148, 1983
Cook DL, Hales CN: Intracellular ATP directly blocks K+ channels in pancreatic B-cells. Nature 311: 271–273, 1984
Spruce AE, Standen NB, Stanfield PR: Voltage-dependent, ATP-sensitive potassium channels of skeletal muscle membrane. Nature 316: 736–738, 1985
Standen NB, Quayle JM, Davies NW, Brayden JE, Huang Y, Nelson MT: Hyperpolarizing vasodilatators activate ATP-sensitive K+ channels in arterial smooth muscle. Science 245: 177–180, 1989
Noma A, Shibasaki T: Membrane current through adenosinetriphosphate-regulated potassium channels in guinea-pig ventricular cells. J Physiol (Lond) 363: 463–480, 1985
Weiss JN, Lamp ST: Glycolysis preferentially inhibits ATP-sensitive K+ current in isolated gluinea-pig cardiac myocytes. Science 238: 67–69, 1987
Cole WC, McPherson CD, Sontag D: ATP-regulated K+ channels protect the myocardium against ischemia/reperfusion demage. Circ Res 69: 571–581, 1991
Rovetto MJ, Whitmer JT, Neely JR: Comparison of the effects of anoxia and whole heart ischaemia on carbohydrate utilization in isolated working rat hearts. Circ Res 32: 699–711, 1973
Weiss JN, Venkatesh N, Lamp ST: ATP-sensitive K+ channels and cellular K+ loss in hypoxic and ischaemic mammalian ventricle. J Physiol 447: 649–673, 1992
Kantor PR, Coetzee WA, Carmeliet EE, Dennis SC, Opie LH: Reduction of ischemic K+ loss and arrhythmias in rat hearts: Effect of glibenclamide, a sulfonylurea. Circ Res 66: 478–485, 1990.
Venkatesh N, Lamp ST, Weiss JN: Effects of sulfonylureas on K+ loss during myocardial ischemia and metabolic inhibition (abstract). Circulation 80 (suppl II): II-607, 1989
Wilde AAM, Escande D, Schumacher CA, Thuringer D, Mestre M, Fiolet JWT, Janse MJ: Potassium accumulation in the globally ischemic mammalian heart: A role for the ATP-sensitive K+ channel. Circ Res 67: 835–843, 1990
Hirano Y, Hiraoka M: Barium-induced automatic activity in isolated ventricular myocytes from guinea-pig hearts. J Physiol 395: 455–472, 1988
Tung RT, Kurachi Y: On the mechanism of nucleotide diphosphate activation of the ATP-sensitive K+ channel in ventricular cell of guinea-pig. J Physiol 437: 239–256, 1991
Gopalakrishnan M, Johnson DE, Janis RA, Triggle DJ: Characterization of binding of the ATP-sensitive potassium channel ligand, [3H]glyburide, to neuronal and muscle preparations. J Pharmacol Exp Ther 257: 1162–1171, 1991
Ripoll C, Lederer WJ, Nichols CG: On the mechanism of inhibition of KATP channels by glibenclamide in rat ventricular cell membranes (abstract). Circulation 82 (suppl IV): III-12, 1990
Venkatesh N, Lamp ST, Weiss JN: Sulfonylureas, ATP-sensitive K+ channels, and cellular K+ loss during hypoxia, ischemia, and metabolic inhibition in mammalian ventricle. Circ Res 69: 623–637, 1991
Findlay I: Inhibition of ATP-sensitive K+ channels in cardiac muscle by the sulfonylurea drug glibenclamide. J Pharmacol Exp Ther 261: 540–545, 1992
Findlay I: ATP4− and ATP·Mg inhibit the ATP-sensitive K+ channel of rat ventricular myocytes. Pflugers Arch 412: 37–41, 1988
Nichols CG, Lederer WJ: The regulation of ATP-sensitive K+ channel activity in intact and permeabilized rat ventricular myocytes. J Physiol (London) 423: 91–110, 1990
Nichols CG, Ripoll C, Lederer WJ: KATP channel modulation of the guinea-pig ventricular action potential and contraction. Circ Res 68: 280–287, 1991
Lederer WJ, Nichols CG: Nucleotide modulation of the activity of rat heart ATP-sensitive K+ channels in isolated membrane patchess. J Physiol 419: 193–211, 1989
Niki I, Nicks JL, Ashcroft SJH: The beta cell glibenclamide receptor is an ADP-binding protein. Biochem J 268: 713–718, 1990
Bernardi H, Fosset M, Lazdunski M: ATP/ADP binding sites are present in the sulfonylurea binding protein associated with brain ATP-sensitive K+ channels. Biochemistry 31: 6328–6332, 1992
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Virág, L., Furukawa, T. & Hiraoka, M. Modulation of the effect of glibenclamide on KATP channels by ATP and ADP. Mol Cell Biochem 119, 209–215 (1993). https://doi.org/10.1007/BF00926873
Issue Date:
DOI: https://doi.org/10.1007/BF00926873