title: Mechanisms regulating spontaneous contractions in the bovine epididymal duct.
abstract: Muscular autorhythmicity provides propulsion of spermatozoa through the epididymal duct, thereby ensuring sperm maturation. In the present study, the mechanisms underlying the bovine epididymal spontaneous phasic contractions (SCs) were analyzed by using muscle-tension recording and patch-clamp techniques. SCs were recorded from the caput, the corpus, and the proximal cauda region and found to be predominantly myogenic in origin. Removal of the luminal fluid induced a burstlike contraction pattern, and removal of the epithelium, a complete loss of SCs. Application of nifedipine, but not heparin and cyclopiazonic acid, suppressed SCs, indicating that influx of Ca2+ through L-type Ca2+ channels, but not Ca2+ release from intracellular stores, was crucial for maintaining SCs. The prostaglandin-endoperoxide synthase 2 (PTGS2) inhibitor NS-398 caused a region-dependent decrease in SCs and tone. These effects were mimicked by the mitogen-activated protein kinase (MAPK) kinase inhibitor PD-98059. Similarly, the prostaglandin F(2alpha) (PGF(2alpha))-receptor antagonist AL-8810 reduced SC generation, whereas PGF(2alpha) induced SC-like activity in epithelium-denuded segments. Cell-isolation experiments revealed the existence of three morphologically different types of contractile cells, which also showed distinct biophysical properties: typical smooth muscle cells in the cauda, myofibroblast-like cells all along the duct, and atypical muscle cells (ATMs) with filament-like spurs in all regions with SCs. These data suggest that the bovine epididymal autorhythmicity is based on an epithelial PTGS2-dependent release of (an) excitatory prostaglandin(s) and a MAPK-dependent activation of L-type Ca2+ channels in the contractile cells. ATM cells may provide electrical coupling between myofibroblasts, which is essential for the generation of regular myogenic activity.
authors.affiliation: Institut für Anatomie II: Experimentelle Morphologie, Zentrum für Experimentelle Medizin, Universitätsklinikum Hamburg-Eppendorf, Universität Hamburg, D-20246 Hamburg, Germany. mewe@uke.uni-hamburg.de
authors.forename: Marco
authors.initials: M
authors.lastname: Mewe
authors.forename: Christiane K
authors.initials: CK
authors.lastname: Bauer
authors.forename: Jürgen R
authors.initials: JR
authors.lastname: Schwarz
authors.forename: Ralf
authors.initials: R
authors.lastname: Middendorff
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism; D015220:Calcium Channels / Q000378:metabolism; D002417:Cattle; D051546:Cyclooxygenase 2 / Q000187:drug effects / Q000378:metabolism; D052246:Cyclooxygenase 2 Inhibitors / Q000494:pharmacology; D015237:Dinoprost / Q000031:analogs & derivatives / Q000494:pharmacology; D004822:Epididymis / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D008297:Male; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D009119:Muscle Contraction / Q000187:drug effects / Q000502:physiology*; D009578:Nitrobenzenes / Q000494:pharmacology; D011453:Prostaglandins / Q000378:metabolism; D013449:Sulfonamides / Q000494:pharmacology
chemical_list: D015220:Calcium Channels; D052246:Cyclooxygenase 2 Inhibitors; D009578:Nitrobenzenes; D011453:Prostaglandins; D013449:Sulfonamides; C080955:N-(2-cyclohexyloxy-4-nitrophenyl)methanesulfonamide; C121227:AL 8810; D015237:Dinoprost; D051546:Cyclooxygenase 2; D020928:Mitogen-Activated Protein Kinases; D002118:Calcium