Aim: 

This study tested the hypothesis that presynaptic neuromodulatory effects of prostaglandin E₁ (PGE₁) are mediated by activation of K⁺ channels in the human isolated vas deferens.

Methods: 

The effects of PGE₁ were studied on isometric contractions induced by noradrenaline and by electrical field stimulation in isolated preparations of the epididymal part of the human vas deferens (n=18). Electrical field stimulation (20 V, 0.25 ms pulse duration, 20 Hz, train duration 5 s, stimulation interval 180 s) produced contractions that were abolished by tetrodotoxin (10^-6 M) and prazosin (10^-6 M).

Results: 

PGE₁ (10^-8 - 10^-6 M) induced concentration-dependent inhibition of electrically-induced adrenergic contractions. Tetraethylammonium (10^-3 M), a nonspecific K⁺ channel blocker, charybdotoxin (10^-7 M), a nonselective inhibitor of voltage-dependent and large- and intermediate-conductance Ca²⁺-activated K⁺ channels, and iberiotoxin (10^-7 M), a selective blocker of large-conductance Ca²⁺-activated K⁺ channels, prevented the inhibitory effects of PGE₁ on the adrenergic contraction. Glibenclamide (10^-5 M), an inhibitor of ATP-sensitive K⁺ channels, and apamin (10^-6 M), a blocker of small-conductance Ca²⁺-activated K⁺ channels, failed to antagonize PGE₁ effects. Pretreatment with PGE₁ (10^-6 M) or iberiotoxin (10^-7 M) did not affect the contractions induced by noradrenaline

Conclusion: 

These results suggest that the presynaptic neuromodulatory action of PGE₁ is mediated by the activation of large-conductance Ca²⁺-activated K⁺ channels. The primary function of the vas deferens is to transport spermatozoa from the epididymis to the ejaculatory duct. Therefore, the reduction in the neurogenic vas deferens contraction by activation of large-conductance Ca²⁺-activated K⁺ channels may induce a decrease in male fertility.

This work was supported by Conselleria de Sanidad (AP-052/08), Generalitat Valenciana.