4-Aminopyridine-induced phasic contractions in rat caudal epididymis are mediated through release of noradrenaline.
4-Aminopyridine, a K+ channel blocker, evoked phasic contractions in the caudal duct of the rat epididymis. The 4-aminopyridine-induced contractile response was either inhibited or prevented by the alpha 1-adrenoceptor antagonists, prazosin (IC50 = 2.7 nM) and benoxathian (IC50 = 14.6 nM). Blockers (1 microM) of alpha 2-adrenoceptors and purinoceptors but not of beta-adrenoceptors or muscarinic receptors caused a small but statistically significant reduction of the 4-aminopyridine-induced response. 4-Aminopyridine lost its ability to induce contractions after noradrenergic nerves had been destroyed by 6-hydroxydopamine. In addition, protriptyline and xylamine, blockers of noradrenaline uptake, also inhibited the 4-aminopyridine-induced contractile response. However, other putative K+ channel blockers (tetraethylammonium ion, quinine, quinidine and glibenclamide) did not cause the muscle to contract. These findings demonstrate that the 4-aminopyridine-induced release of noradrenaline and adenosine 5'-triphosphate as co-transmitters results from membrane depolarization due to 4-aminopyridine blockade of K+ channels in noradrenergic nerve terminals. The 4-aminopyridine-sensitive K+ channels might thus play a physiological role in regulating the nerve membrane potential and neurotransmission in the rat caudal epididymis.
Huang
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Department of Physiology, Chinese University of Hong Kong, Shatin, NT.
D015761:4-Aminopyridine / Q000494:pharmacology*; D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D004822:Epididymis / Q000187:drug effects* / Q000294:innervation / Q000378:metabolism; D066298:In Vitro Techniques; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects* / Q000294:innervation / Q000378:metabolism; D009638:Norepinephrine / Q000378:metabolism*; D016627:Oxidopamine; D015221:Potassium Channels / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013563:Sympathectomy, Chemical; D013564:Sympathetic Nervous System / Q000187:drug effects; D009435:Synaptic Transmission / Q000187:drug effects
D015221:Potassium Channels; D016627:Oxidopamine; D000255:Adenosine Triphosphate; D015761:4-Aminopyridine; D009638:Norepinephrine