ATP-Dependent Activation of the Atrial Acetylcholine-Induced K⁺ Channel Does Not Require Nucleoside Diphosphate Kinase Activity

From the Department of Pharmacology (S.S., X.-Y.D.), Columbia University, New York, NY, and Wyeth Ayerst Research (M.C., M.K.), Princeton, NJ.

Correspondence to Steve Sorota, PhD, Department of Pharmacology, Columbia University, 630 West 168th St, New York, NY 10032. E-mail ss47{at}columbia.edu

Abstract—Prior reports by others have shown that cytoplasmically applied ATP can activate the acetylcholine-induced K⁺ channel in inside-out atrial membrane patches when no guanine nucleotides are present in the solution bathing the cytosolic face of the membrane. A nucleoside diphosphate kinase mechanism was proposed to explain the activation by ATP. We show in the present study that cytoplasmic adenylylimidodiphosphate mimics the activation by ATP. Unlike ATP, the activation by adenylylimidodiphosphate does not subside on washout. Although commercially available adenylylimidodiphosphate is contaminated by guanylylimidodiphosphate, the activation by adenylylimidodiphosphate still occurs after HPLC purification to remove guanine nucleotide contamination. Adenylylimidodiphosphate does not support phosphotransferase activity by nucleoside diphosphate kinase. Therefore, nucleoside diphosphate kinase activity cannot explain the activation of atrial acetylcholine-induced K⁺ current by ATP and adenylylimidodiphosphate. We hypothesize that the activation by millimolar concentrations of ATP is due to binding of adenine nucleotide to the guanine nucleotide binding site of the G protein(s) responsible for stimulating the acetylcholine-induced K⁺ current.

Key Words: acetylcholine-induced K⁺ channel • adenylylimidodiphosphate • ATP • atrial myocyte • nucleoside diphosphate kinase

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