흰쥐 감각신경원의 소디움 전류에 대한Fluoxetine의 효과

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 informa-tion 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 cur-rents 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 μM and 59 μM, 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 block-ade of sodium currents in sensory neurons is considered as a possible mechanism for the analgesic action of fluoxetine.J Korean Neurol Assoc 18(6):754~763, 2000Key Words : Fluoxetine, Tetrodotoxin, Sodium channel, Pain, Dorsal root ganglion, Patch clamp