Effects of Fluoxetine on Sodium Currents in Rat Sensory Neurons.
- Author:
Hyun Wook HA
1
;
Jeong Ho HAN
;
Yoon Young JANG
;
Yong Kyoo SHIN
;
Chung Soo LEE
;
Jin Ho SONG
Author Information
1. Department of Pharmacology, ChungAng University College of Medicine.
- Publication Type:Original Article
- Keywords:
Fluoxetine;
Tetrodotoxin;
Sodium channel;
Pain;
Dorsal root ganglion;
Patch clamp
- MeSH:
Animals;
Central Nervous System;
Diagnosis-Related Groups;
Digestion;
Fluoxetine*;
Ganglia, Spinal;
Neurons;
Nociception;
Rats*;
Sensory Receptor Cells*;
Serotonin;
Sodium Channels;
Sodium*;
Tetrodotoxin
- From:Journal of the Korean Neurological Association
2000;18(6):754-763
- CountryRepublic of Korea
- Language:Korean
-
Abstract:
BACKGROUND: Fluoxetine, a widely used antidepressant drug, has been described as a selective serotonin reuptake inhibitor. In addition to its antidepressant action it has been demonstrated to be effective in alleviating pain associated with various diseases. Dorsal root ganglion (DRG) neurons are primary sensory neurons and transmit peripheral information to central nervous system. Two types of sodium channels are expressed in DRG neurons based on their sensitivity to tetrodotoxin. They are involved in the generation and conduction of nociception. The effects of fluoxetine on sodium currents in DRG neurons were examined to elucidate the analgesic mechanism of the drug. METHODS: DRG neurons wereacutely dissociated from rats (2~6 days postnatal) by enzymatic digestion. The whole-cell configuration of patch clamp technique was used to record tetrodotoxin-sensitive (TTX-S) and tetrodotoxin-resistant (TTX-R) sodium currents. RESULTS: Fluoxetine inhibited TTX-S and TTX-R sodium currents with Kd values of 60 microM and 59 microM, respectively, at the holding potential of -80 mV. For both types of sodium channels the steady-state inactivation curves were shifted in the hyperpolarizing direction and the conductance-voltage relationship curves were shifted in the depolarizing direction by fluoxetine. These effects combined together would greatly reduce the neuronal excitability. CONCLUSIONS: The blockade of sodium currents in sensory neurons is considered as a possible mechanism for the analgesic action of fluoxetine.
