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

  • Organ physiology
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Abstract

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 Ca2+ channel (LVDCC) blocker nifedipine (1 μM), with the T-type voltage-dependent Ca2+ channel (TVDCC) blocker ML218 (1 μM) specifically decreasing SPC frequency. SPCs were inhibited upon blockade of the SR/ER Ca2+-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 α1-adrenoceptor-sensitive contraction in distal segments and enhanced and/or induced α2-adrenoceptor-sensitive oscillatory phasic contractions in proximal and distal segments, the latter mimicked by application of the α2-adrenoceptor agonist clonidine. We hypothesise that SPCs in the proximal cauda are triggered by pacemaker mechanisms involving rhythmic IP3 receptor–operated SR/ER store Ca2+ release and resultant activation of CaCC with TVDCCs and possibly LVDCCs subserving in this process. Sympathetic nerve-released noradrenaline induces α2-adrenoceptor-mediated phasic contractions in the proximal and distal cauda. These findings provide new pharmacological targets for male infertility and contraception.

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Data availability

Data is available on demand from Professor Hikaru Hashitani in whose laboratory this research was undertaken.

Abbreviations

2-APB: :

2-Aminoethoxydiphenyl borate

α-SMA:

α-Smooth muscle actin

BSS:

Buffered saline solution

CaCC:

Calcium-activated chloride channels

CPA:

Cyclopiazonic acid

DMSO:

Dimethyl sulphoxide

EFS:

Electrical field stimulation

ET-1:

Endothelin 1

LVDCC:

L-type voltage-dependent Ca2+ channel

IgG:

Immunoglobulin G

SPCs:

Spontaneous phasic contractions

SR/ER:

Sarcoendoplasmic reticulum

TH:

Tyrosine hydroxylase

TVDCC:

T-type voltage-dependent Ca2+ channel

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Funding

The present study was partly supported by Grant-in-Aid for Scientific Research (C) (No. 19K08426) from Japan Society for Promotion of the Science (JSPS) to R.M.

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Authors and Affiliations

  1. Department of Cell Physiology, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan

    Retsu Mitsui & Hikaru Hashitani

  2. Department of Physiology, Faculty of Medicine, Nursing and Health Sciences, School of Biomedical Sciences, Monash University, Clayton, Australia

    Richard J. Lang

  3. School of Biomedical Sciences and Pharmacy and Hunter Medical Research Institute, Faculty of Health and Medicine, The University of Newcastle, Callaghan, NSW, 2308, Australia

    Dirk F. van Helden

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  1. Retsu Mitsui
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  2. Hikaru Hashitani
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  3. Richard J. Lang
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  4. Dirk F. van Helden
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Contributions

Conceptualization: HH, DVH; methodology: HH, RL, RM, DVH; formal analysis and investigation: HH, RM, DVH; writing—review and editing: HH, RL, RM, DVH.

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Correspondence to Dirk F. van Helden.

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Mitsui, R., Hashitani, H., Lang, R.J. et al. Mechanisms underlying spontaneous phasic contractions and sympathetic control of smooth muscle in the rat caudal epididymis. Pflugers Arch - Eur J Physiol 473, 1925–1938 (2021). https://doi.org/10.1007/s00424-021-02609-z

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