title: Verapamil, a phenylalkylamine Ca2+ channel blocker, inhibits ATP-sensitive K+ channels in insulin-secreting cells from rats.
abstract: Radioisotopic and electrophysiological techniques were used to assess the effects of verapamil, a phenylalkylamine Ca2+ channel blocker, on K+ permeability of insulin-secreting cells. Verapamil provoked a concentration-dependent inhibition of 86Rb (42K substitute) outflow from prelabelled and perifused rat pancreatic islets. This property appears to be inherent to the phenylalkylamine Ca2+ channel blockers since gallopamil, a methoxyderivative of verapamil, but not nifedipine, a 1,4-dihydropyridine Ca2+ channel blocker, inhibited 86Rb outflow. The experimental data further revealed that verapamil interacted with a Ca2+-independent, glucose- and glibenclamide-sensitive modality of 86Rb extrusion. Moreover, verapamil prevented the increase in 86Rb outflow brought about by BPDZ 44; a potent activator of the ATP-sensitive K+ channel. Single-channel current recordings by the patch clamp technique confirmed that verapamil elicited a dose-dependent inhibition of the ATP-dependent K+ channel. Lastly, under experimental conditions in which verapamil clearly inhibited the ATP-sensitive K+ channels, the drug did not affect 45Ca outflow, the cytosolic free Ca2+ concentration or insulin release. It is concluded that the Ca2+ entry blocker verapamil inhibits ATP-sensitive K+ channels in pancreatic beta cells. This effect was not associated with stimulation of insulin release.
authors.affiliation: Laboratory of Pharmacology, Faculty of Medicine, Université Libre de Bruxelles, Brussels, Belgium.
authors.forename: P
authors.initials: P
authors.lastname: Lebrun
authors.forename: M H
authors.initials: MH
authors.lastname: Antoine
authors.forename: R
authors.initials: R
authors.lastname: Ouedraogo
authors.forename: B
authors.initials: B
authors.lastname: Pirotte
authors.forename: A
authors.initials: A
authors.lastname: Herchuelz
authors.forename: K E
authors.initials: KE
authors.lastname: Cosgrove
authors.forename: C
authors.initials: C
authors.lastname: Kane
authors.forename: M J
authors.initials: MJ
authors.lastname: Dunne
mesh_terms: D000255:Adenosine Triphosphate / Q000494:pharmacology*; D000818:Animals; D002118:Calcium / Q000378:metabolism; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D002132:Calcium Radioisotopes / Q000378:metabolism; D005260:Female; D005711:Gallopamil / Q000494:pharmacology; D005947:Glucose / Q000494:pharmacology; D005905:Glyburide / Q000494:pharmacology; D007004:Hypoglycemic Agents / Q000494:pharmacology; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000187:drug effects / Q000378:metabolism*; D026902:Potassium Channel Blockers; D015221:Potassium Channels / Q000187:drug effects; D011725:Pyridines / Q000494:pharmacology; D051381:Rats; D012414:Rubidium Radioisotopes / Q000378:metabolism; D013829:Thiadiazines / Q000494:pharmacology; D014700:Verapamil / Q000494:pharmacology*
chemical_list: D002121:Calcium Channel Blockers; D002132:Calcium Radioisotopes; D007004:Hypoglycemic Agents; D007328:Insulin; D026902:Potassium Channel Blockers; D015221:Potassium Channels; D011725:Pyridines; D012414:Rubidium Radioisotopes; D013829:Thiadiazines; C087201:BPDZ 44; D005711:Gallopamil; D000255:Adenosine Triphosphate; D014700:Verapamil; D005947:Glucose; D005905:Glyburide; D002118:Calcium