Effects of Fluoxetine on Membrane Potential and Ionic Currents in RINm5F Insulinoma Cells

Park, Ki Chang; Oh, Guk Taek; Cha, Seung Kyu; Lee, Keon Il; Park, Kyu Sang; Jeong, Seong Woo; Kong, In Deok; Lee, Joong Woo

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.