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  • Title: Disopyramide blocks pancreatic ATP-sensitive K+ channels and enhances insulin release.
    Author: Hayashi S, Horie M, Tsuura Y, Ishida H, Okada Y, Seino Y, Sasayama S.
    Journal: Am J Physiol; 1993 Aug; 265(2 Pt 1):C337-42. PubMed ID: 8368263.
    Abstract:
    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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