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

P. Lebrun, M. H. Antoine, R. Ouedraogo, B. Pirotte, A. Herchuelz, K. E. Cosgrove, C. Kane, M. J. Dunne

    Research output: Contribution to journalArticlepeer-review

    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 .
    Original languageEnglish
    Pages (from-to)1403-1410
    Number of pages7
    JournalDiabetologia
    Volume40
    Issue number12
    DOIs
    Publication statusPublished - 1997

    Keywords

    • ATP-sensitive K+ channel
    • Insulin release
    • Rat pancreatic beta cells
    • Verapamil

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