Disopyramide blocks pancreatic ATP-sensitive K+ channels and enhances insulin release.
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.
Hayashi
S
S
Department of Physiology, Faculty of Medicine, Kyoto University, Japan.
Horie
M
M
Tsuura
Y
Y
Ishida
H
H
Okada
Y
Y
Seino
Y
Y
Sasayama
S
S
D000255:Adenosine Triphosphate / Q000494:pharmacology*; D000818:Animals; D004206:Disopyramide / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004594:Electrophysiology / Q000379:methods; D005905:Glyburide / Q000378:metabolism / Q000494:pharmacology; D066298:In Vitro Techniques; D007328:Insulin / Q000378:metabolism*; D007515:Islets of Langerhans / Q000378:metabolism*; D008297:Male; D009994:Osmolar Concentration; D015221:Potassium Channels / Q000187:drug effects* / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar
D007328:Insulin; D015221:Potassium Channels; D000255:Adenosine Triphosphate; D004206:Disopyramide; D005905:Glyburide