Effect of fluoxetine on calcium or potassium channels in the neuron of rat major pelvic ganglia

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 10.8 μM, 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 3.2 μM. 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.