Verapamil, a phenylalkylamine Ca2+ channel blocker, inhibits ATP-sensitive K+ channels in insulin-secreting cells from rats

Diabetologia. 1997 Dec;40(12):1403-10. doi: 10.1007/s001250050842.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenosine Triphosphate / pharmacology*
  • Animals
  • Calcium / metabolism
  • Calcium Channel Blockers / pharmacology*
  • Calcium Radioisotopes / metabolism
  • Female
  • Gallopamil / pharmacology
  • Glucose / pharmacology
  • Glyburide / pharmacology
  • Hypoglycemic Agents / pharmacology
  • Insulin / metabolism*
  • Insulin Secretion
  • Islets of Langerhans / drug effects
  • Islets of Langerhans / metabolism*
  • Potassium Channel Blockers*
  • Potassium Channels / drug effects
  • Pyridines / pharmacology
  • Rats
  • Rubidium Radioisotopes / metabolism
  • Thiadiazines / pharmacology
  • Verapamil / pharmacology*

Substances

  • Calcium Channel Blockers
  • Calcium Radioisotopes
  • Hypoglycemic Agents
  • Insulin
  • Potassium Channel Blockers
  • Potassium Channels
  • Pyridines
  • Rubidium Radioisotopes
  • Thiadiazines
  • BPDZ 44
  • Gallopamil
  • Adenosine Triphosphate
  • Verapamil
  • Glucose
  • Glyburide
  • Calcium