Fluoxetine이 흰쥐 주골반신경절 신경세포에 존재하는 칼슘 및 포타슘 통로에 미치는 영향

Abstract

Purpose: The major pelvic ganglia (MPG) provide the majority of the innervations to the lower urinary tract. The pelvic ganglia are unique autonomic ganglia that contain both sympathetic and parasympathetic neurons. It has been known that the low-threshold voltage-gated (T-type) Ca2 channels are only expressed only in the sympathetic neurons, whereas these channels are absent in parasympathetic neurons. In the present study, we examined the effect of fluoxetine, a world-wide used antidepressant, on the voltage-dependent Ca2 and K currents in the adrenergic neurons of the MPG. Materials and Methods: The effect of fluoxetine on the voltage-dependent Ca2 and K currents in the adrenergic neurons of the MPG were examined using the whole-cell patch-clamp technique. Results: Fluoxetine inhibited the voltage-activated Ca2 currents in the adrenergic neurons of the MPG. Both high-threshold (HVA) and low- threshold (LVA, T-type) Ca2 currents were inhibited by fluoxetine with an IC50 of 5.3 and 10.8mum, respectively. Fluoxetine also decreased the both the peak amplitude and the plateau of the outward K currents. The inhibition of the peak K currents by fluoxetine was concentration- dependent with an IC50 of 3.2mum. The inhibitions of the Ca2 and K currents were quickly reversible upon washout of the fluoxetine. Conclusions: These results provide evidence for the direct inhibition of the voltage dependant Ca2 and K currents by fluoxetine and these inhibitory effects could modify the synaptic transmission in adrenergic neurons of the MPG. (Korean J Urol 2005;46:626-631) Key Words: Autonomic ganglia, Fluoxetine, Calcium channel, Potassium channel