COMPARATIVE-STUDY OF THE EFFECTS OF CROMAKALIM (BRL-34915) AND DIAZOXIDE ON MEMBRANE-POTENTIAL, [CA-2+]I AND ATP-SENSITIVE POTASSIUM CURRENTS IN INSULIN-SECRETING CELLS

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±6n m (n=37), glucose (2.5-10 mm): (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. © 1990 Springer-Verlag New York Inc.