Mechanisms underlying spontaneous phasic contractions and sympathetic control of smooth muscle in the rat caudal epididymis.

Here we investigate mechanisms underlying spontaneous phasic contractions (SPCs) and sympathetic control of contractility in the rat epididymis, a long tubular duct involved in transportation and maturation of sperm. Longitudinal contractions of short segments (~ 1.5 mm) of rat proximal and distal caudal epididymal duct were measured + / - nerve stimulation. The extent of sympathetic innervation of these duct regions was determined by immunohistochemistry. Proximal caudal duct segments (150-300 μm dia.) exhibited SPCs, while distal segments (350-500 μm) were quiescent in ~ 80% of preparations. SPC amplitude and frequency were reduced by the L-type voltage-dependent Ca channel (LVDCC) blocker nifedipine (1 μM), with the T-type voltage-dependent Ca channel (TVDCC) blocker ML218 (1 μM) specifically decreasing SPC frequency. SPCs were inhibited upon blockade of the SR/ER Ca-ATPase (CPA 10 μM). SPCs were also inhibited by caffeine (1 μM), 2-APB (100 μM), niflumic acid (100 μM), or by lowering extracellular [Cl] from 134.4 to 12.4 mM but not by ryanodine (25 μM) or tetracaine (100 μM). Electrical field stimulation (EFS) at 2 Hz for 60 s caused a sustained α-adrenoceptor-sensitive contraction in distal segments and enhanced and/or induced α-adrenoceptor-sensitive oscillatory phasic contractions in proximal and distal segments, the latter mimicked by application of the α-adrenoceptor agonist clonidine. We hypothesise that SPCs in the proximal cauda are triggered by pacemaker mechanisms involving rhythmic IP receptor-operated SR/ER store Ca release and resultant activation of CaCC with TVDCCs and possibly LVDCCs subserving in this process. Sympathetic nerve-released noradrenaline induces α-adrenoceptor-mediated phasic contractions in the proximal and distal cauda. These findings provide new pharmacological targets for male infertility and contraception.