Effects of acetylcholinesterase inhibitor paraoxon denote the possibility of non-quantal acetylcholine release in myocardium of different vertebrates
Effects of acetylcholinesterase inhibitor paraoxon denote the possibility of non-quantal acetylcholine release in myocardium of different vertebrates
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DOI：
10.1007/s00360-011-0602-2
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发表时间：
2012-01-01
期刊：
影响因子：
--
通讯作者：
Rosenshtraukh, Leonid V.
中科院分区：
文献类型：
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作者：
Abramochkin, Denis V.;Borodinova, Anastasia A.;Rosenshtraukh, Leonid V.
用微电极技术研究了乙酰胆碱酯酶抑制剂对氧磷对鱼类、两栖类和哺乳类离体心房和心室肌的作用。用对氧磷（5 × 10（-6）~ 5 × 10（-5）M）孵育离体心房，引起动作电位时程显著缩短，窦性心律明显减慢。这些作用被毒蕈碱阻断剂阿托品消除，因此是由乙酰胆碱引起的，乙酰胆碱在心肌中蓄积是由于乙酰胆碱酯酶抑制，即使在没有迷走神经输入的情况下。Hemicholinium III是高亲和力胆碱摄取转运蛋白的阻断剂，其被认为介导乙酰胆碱从不同组织中的胆碱能末端的非量子释放。在所有三种研究物种的心房心肌中，hemicholinium III（10（-5）M）显著抑制对氧磷的所有作用。副交感神经节传递阻滞剂溴化六甲双铵（10（-4）M）和囊泡乙酰胆碱转运体抑制剂维索霉素（10（-5）M）不能减弱对氧磷的作用。在心室肌制备的三种对氧磷引起显着的胆碱能作用，只有在青蛙，hemicholinium III有效地消除了这些影响。我们的结论是，对氧磷停止在心肌中的乙酰胆碱的降解，并有助于揭示乙酰胆碱，这是连续分泌的胆碱能神经在非量子方式的影响。因此，心脏中乙酰胆碱的非量子释放不仅是哺乳动物特有的，而且也存在于不同脊椎动物的心脏中。
Effects of organophosphorous acetylcholinesterase inhibitor paraoxon were studied in the isolated atrial and ventricular myocardium preparations of a fish (cod), an amphibian (frog) and a mammal (rat) using the microelectrode technique. Incubation of isolated atrium with paraoxon (5 x 10(-6)-5 x 10(-5) M) caused significant reduction of action potential duration and marked slowing of sinus rhythm. These effects were abolished by muscarinic blocker atropine and therefore are caused by acetylcholine, which accumulates in the myocardium due to acetylcholinesterase inhibition even in the absence of vagal input. Hemicholinium III is a blocker of high affinity choline-uptake transporters, which are believed to mediate non-quantal release of acetylcholine from cholinergic terminals in different tissues. In the atrial myocardium of all the three studied species, hemicholinium III (10(-5) M) significantly suppressed all the effects of paraoxon. Blocker of parasympathetic ganglionic transmission hexamethonium bromide (10(-4) M) and inhibitor of vesicular acetylcholine transporters vesamicol (10(-5) M) failed to attenuate paraoxon effects. Among ventricular myocardium preparations of three species paraoxon provoked marked cholinergic effects only in frog, hemicholinium III abolished these effects effectively. We conclude that paraoxon stops degradation of acetylcholine in the myocardium and helps to reveal the effects of acetylcholine, which is continuously secreted from the cholinergic nerves in non-quantal manner. Thus, non-quantal release of acetylcholine in the heart is not specific only for mammals, but is also present in the hearts of different vertebrates.