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Korean Journal of Psychopharmacology ; : 233-241, 2001.
Article in Korean | WPRIM | ID: wpr-153167

ABSTRACT

OBJECTIVE: The purpose of this study was to investigate the effects of fluoxetine (Prozac) on membrane potential and ionic currents in RINm5F insulinoma cells. METHODS: Membrane potential and ionic currents in RINm5F cell were recorded by using whole-cell and perforated-patch clamp techniques. RESULTS: Under current clamp conditions, diazoxide (200 microM), an activator of K ATP channels, induced a hyperpolarization of the resting membrane potential (-16.1+/-1.4 mV, n=), which was accompanied by a abolition of action potential firing. This diazoxide-induced hyperpolarization was blocked by glibenclamide (10 microM). Fluoxetine produced significant depolarization of membrane potential (15.9+/-3.1 mV, n=) and blocked diazoxide-induced hyperpolarization. Diazoxide activated inward currents in the presence of high external K + (90 mM) at a holding potential of -60 mV. Fluoxetine suppressed diazoxide-activated currents in a concentration-dependent (IC 50 =.84 microM) manner. However, the inhibitory action of fluoxetine was not specific to K ATP currents because it also inhibited both voltage-activated K + and Ca 2+ currents in a concentration-dependent manner. K ATP currents were more sensitive to fluoxetine block than both voltage-activated K + and Ca 2+ currents. CONCLUSION: Our results indicate that fluoxetine increased excitability of RINm5F cells mainly by the preferential block of K ATP currents. Fluoxetine-induced depolarization may influence insulin secretion in insulinoma cells.


Subject(s)
Action Potentials , Adenosine Triphosphate , Diazoxide , Fires , Fluoxetine , Glyburide , Insulin , Insulinoma , Membrane Potentials , Membranes
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