Effects of Fluoxetine on Membrane Potential and Ionic Currents in RINm5F Insulinoma Cells.
- Author:
Ki Chang PARK
1
;
Guk Taek OH
;
Seung Kyu CHA
;
Keon Il LEE
;
Kyu Sang PARK
;
Seong Woo JEONG
;
In Deok KONG
;
Joong Woo LEE
Author Information
1. Department of Psychiatry, Yonsei University Wonju College of Medicine, Wonju, Korea.
- Publication Type:Original Article
- Keywords:
Fluoxetine;
K ATP channel;
Membrane potential;
Ionic current;
Insulin secretion
- MeSH:
Action Potentials;
Adenosine Triphosphate;
Diazoxide;
Fires;
Fluoxetine*;
Glyburide;
Insulin;
Insulinoma*;
Membrane Potentials*;
Membranes*
- From:Korean Journal of Psychopharmacology
2001;12(3):233-241
- CountryRepublic of Korea
- Language:Korean
-
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.
