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.
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 +/- 6 nM (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 microM) and diazoxide (100 microM) 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.
Dunne
M J
MJ
MRC Secretory Control Research Group, Physiological Laboratory, University of Liverpool, England.
Yule
D I
DI
Gallacher
D V
DV
Petersen
O H
OH
D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D001578:Benzopyrans / Q000494:pharmacology*; D002118:Calcium / Q000378:metabolism*; D002460:Cell Line; D019806:Cromakalim; D003981:Diazoxide / Q000494:pharmacology*; D005947:Glucose / Q000494:pharmacology; D007515:Islets of Langerhans / Q000187:drug effects* / Q000378:metabolism; D007700:Kinetics; D008564:Membrane Potentials / Q000187:drug effects; D015221:Potassium Channels / Q000187:drug effects*; D011758:Pyrroles / Q000494:pharmacology*; D014044:Tolbutamide / Q000494:pharmacology
D001578:Benzopyrans; D015221:Potassium Channels; D011758:Pyrroles; D019806:Cromakalim; D000255:Adenosine Triphosphate; D014044:Tolbutamide; D005947:Glucose; D003981:Diazoxide; D002118:Calcium