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The Journal of Membrane Biology

, Volume 114, Issue 1, pp 53–60 | Cite as

Comparative study of the effects of cromakalim (BRL 34915) and diazoxide on membrane potential, [Ca2+] i and ATP-sensitive potassium currents in insulin-secreting cells

  • M. J. Dunne
  • D. I. Yule
  • D. V. Gallacher
  • O. H. Petersen
Articles

Summary

Patch-clamp and single cell [Ca2+] i measurements have been used to investigate the effects of the potassium channel modulators cromakalim, diazoxide and tolbutamide on the insulin-secreting cell line RINm5F. In intact cells, with an average cellular transmembrane potential of −62±2 mV (n=42) and an average basal [Ca2+] i of 102±6nm (n=37), glucose (2.5–10mm): (i) depolarized the membrane, through a decrease in the outward KATP current, (ii) evoked Ca2+ spike potentials, and (iii) caused a sharp rise in [Ca2+] i . In the continued presence of glucose both cromakalim (100–200 μm) and diazoxide (100 μm) repolarized the membrane, terminated Ca2+ spike potentials and attenuated the secretagogue-induced rise in [Ca2+] i . In whole cells (voltage-clamp records) and excised outside-out membrane patches, both cromakalim and diazoxide enhanced the current by opening ATP-sensitive K+ channels. Diazoxide was consistently found to be more potent than cromakalim. Tolbutamide, a specific inhibitor of ATP-sensitive K+ channels, reversed the effects of cromakalim on membrane potential and KATP currents.

Key Words

patch-clamp fura-2 KATP channels [Ca2+]i insulin-secreting cell RINm5F cell diazoxide cromakalim (BRL 34915) tolbutamide 

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Copyright information

© Springer-Verlag New York Inc 1990

Authors and Affiliations

  • M. J. Dunne
    • 1
  • D. I. Yule
    • 1
  • D. V. Gallacher
    • 1
  • O. H. Petersen
    • 1
  1. 1.The MRC Secretory Control Research Group, Physiological LaboratoryUniversity of LiverpoolLiverpoolEngland

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