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 |
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Authors: | M. J. Dunne D. I. Yule D. V. Gallacher O. H. Petersen |
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Affiliation: | (1) The MRC Secretory Control Research Group, Physiological Laboratory, University of Liverpool, L69 3BX Liverpool, England |
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Abstract: | 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 m) and diazoxide (100 m) 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. |
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Keywords: | patch-clamp fura-2 KATP channels [Ca2+]i insulin-secreting cell RINm5F cell diazoxide cromakalim (BRL 34915) tolbutamide |
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