Although parasympathetic regulation is extremely important for normal functioning of the mammalian heart, little is known about its secretion from the parasympathetic nerve terminals in the myocardium. It is accepted that in the neuromuscular junction acetylcholine (ACh) may be released from the nerve terminal by quantal or non-quantal type of secretion. The non-quantal release in the neuromuscular junction may be detected due to the slight depolarization of the muscle fiber during inhibition of acetylcholinesterase (AChE). Nothing is known about the existence of non-quantal release in the heart.

We have used the conventional microelectrode technique to register changes of action potential (AP) configuration in the isolated preparation of rat right atrium during the application of AChE inhibitors. AChE inhibitors armin (10^-7-10^-5M) and neostigmine (10^-7-5·10^-6M) provoked typical cholinergic effects: reduction of AP duration and prolongation of the cycle length. These effects were abolished by atropine, therefore they are mediated by ACh, accumulated in the myocardium during AChE inhibition. These results beg the question of what is the mechanism of AChs release in isolated atrium preparation, where the impulse activity of vagus is absent. Three ways of mediator secretion are known at present: evoked quantal release associated with excitation of neuron, spontaneous quantal release and finally, non-quantal release.

Putative block of postganglionic neurons impulse activity by tetrodotoxin (2·10^-7M) and hexomethonium (10^-5M) as well as the block of all forms of quantal release with botulinic toxin type A (50 U/ml) didn't alter effects of armin. Experiments with lipophilic fluorescent dye FM1-43 confirmed the presence of endocytosis in cholinergic fibers, crucial for the effective block of exocytosis by botulinic toxin. Therefore, accumulation of ACh doesn't depend on evoked or spontaneous quantal release. Selective inhibitor of choline uptake system hemicholinium III (10^-5M), which blocks non-quantal release in the neuromuscular junction, suppressed all effects of AChE inhibitors. Therefore, accumulation of ACh in the myocardium during inhibition of AChE is likely to be caused by the non-quantal release of ACh from the cholinergic terminals.

Thus, non-quantal release of ACh, shown earlier in the neuromuscular junction, is present in the cholinergic postganglionic fibers of the rat heart in addition to quantal release.