AJP - Cell Physiology, Vol 265, Issue 2 C337-C342, Copyright © 1993 by American Physiological Society

ARTICLES

Disopyramide blocks pancreatic ATP-sensitive K+ channels and enhances insulin release

S. Hayashi, M. Horie, Y. Tsuura, H. Ishida, Y. Okada, Y. Seino and S. Sasayama
Department of Physiology, Faculty of Medicine, Kyoto University, Japan.

An antiarrhythmic agent, disopyramide, was found to enhance the insulin secretory capacity of Wistar rat pancreatic islets with a half-maximal concentration of 23.3 microM. Employing a patch-clamp technique, disopyramide was found to inhibit ATP-sensitive K+ (KATP) channel activity in rat pancreatic beta-cells in primary culture without altering the unitary conductance. Half-maximal inhibition was achieved by the addition of 3.6 microM disopyramide to the intracellular bathing solution in the inside-out mode, 11.0 microM to the extracellular bathing solution in the outside-out mode, and 87.4 microM in the cell-attached mode. The binding of [3H]glibenclamide to pancreatic islets was inhibited by unlabeled glibenclamide but not by unlabeled disopyramide. Based on these observations, it is concluded that disopyramide blocks pancreatic KATP channels via binding to a site(s) distinct from the sulfonylurea receptor. This effect may be causatively involved in disopyramide-induced hypoglycemia.

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