Voltage-activated Na+ currents and their suppression by phorbol ester in clonal insulin-producing RINm5F cells.
The whole-cell configuration of the patch-clamp technique was applied on the clonal insulin-producing cell line RINm5). Thus attempts were made to characterize voltage-activated inward and outward membrane currents and to examine to what extent these were affected by both long-term and acute exposure to the phorbol ester 12-O-tetradecanoylphorbol-13-acetate (TPA). Current responses to voltage-clamp steps up to -40 mV were small. A pulse to -28 mV evoked an inward current, and slowly activating outward currents developed at potentials above -20 mV. The inward current had a V-shaped current-voltage relationship, reaching a peak between -10 and 0 mV, whereas the outward current increased linearly at potentials beyond -20 mV. It was demonstrated that the inward currents are carried primarily by Ca2+ and Na+ and the outward current by K+. After long-term exposure to TPA, there was a suppression of Na+ currents in one-third of the cells, whereas the Ca2+ and K+ currents were unaffected. Acute exposure to the phorbol ester increased the Ca2+ currents with little effect on the Na+ currents. The extent to which the differences in effects on membrane currents initiated by respective acute and long-term exposure to TPA may reflect two separate mechanisms of protein kinase C activation, the latter related to regulation of differentiation of the RINm5F cells, merits further investigation.
D000200:Action Potentials / Q000187:drug effects; D007516:Adenoma, Islet Cell / Q000503:physiopathology*; D000818:Animals; D002118:Calcium / Q000378:metabolism; D002460:Cell Line; D002999:Clone Cells; D007328:Insulin / Q000378:metabolism; D000078790:Insulin Secretion; D007340:Insulinoma / Q000503:physiopathology*; D007473:Ion Channels / Q000187:drug effects / Q000502:physiology*; D008564:Membrane Potentials; D010190:Pancreatic Neoplasms / Q000503:physiopathology*; D051381:Rats; D012964:Sodium / Q000378:metabolism*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology*
D007328:Insulin; D007473:Ion Channels; D012964:Sodium; D013755:Tetradecanoylphorbol Acetate; D002118:Calcium