Effect of Fluoxetine on Calcium or Potassium Channels in the Neuron of Rat Major Pelvic Ganglia Innervating the Lower Urinary Tract Organs

Abstract

Pelvic ganglia provide the majority of the innervations of the lower urinary tract including erection or ejaculation. Major pelvic ganglia (MPG) in rats are unique autonomic ganglia, containing both sympathetic and parasympathetic neurons. It has been known that the low-threshold voltage-gated (T-type) Ca2+ channels are expressed only in the sympathetic neurons, whereas lacked in parasympathetic neurons. In the present study we examined the effect of fluoxetine, a world-wide used antidepressant, on voltage-dependent Ca2+ and K+ currents in the sympathetic neurons of MPG using whole-cell patch-clamp technique. Fluoxetine inhibited voltage-activated Ca2+ currents in sympathetic neurons of 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 M, respectively. Fluoxetine also decreased the both peak amplitude and plateau of outward K+ currents. The inhibition of peak K+ currents by fluoxetine was concentration-dependent with an IC50 of 3.2 μM. The inhibitions of Ca2+ and K+ currents were quickly reversible upon washout of fluoxetine. These results provide evidence for the direct inhibition of voltage dependant Ca2+ and K+ currents by fluoxetine and these inhibitory effects could modify synaptic transmission in sympathetic neurons of MPG. It is suggested that the inhibition of ion currents in MPG by fluoxetine can have the direct effects on erection or ejaculation. Fluoxetine inhibited voltage-activated Ca2+ currents in sympathetic neurons of 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 M, respectively. Fluoxetine also decreased the both peak amplitude and plateau of outward K+ currents. The inhibition of peak K+ currents by fluoxetine was concentration-dependent with an IC50 of 3.2 μM. The inhibitions of Ca2+ and K+ currents were quickly reversible upon washout of fluoxetine. These results provide evidence for the direct inhibition of voltage dependant Ca2+ and K+ currents by fluoxetine and these inhibitory effects could modify synaptic transmission in sympathetic neurons of MPG. It is suggested that the inhibition of ion currents in MPG by fluoxetine can have the direct effects on erection or ejaculation. These results provide evidence for the direct inhibition of voltage dependant Ca2+ and K+ currents by fluoxetine and these inhibitory effects could modify synaptic transmission in sympathetic neurons of MPG. It is suggested that the inhibition of ion currents in MPG by fluoxetine can have the direct effects on erection or ejaculation.