Aims: In mammalian myocardium acetylcholine (ACh), neurotransmitter which strikingly affects the cardiomyocytes, can be released from the neurons both via quantal (vesicular) and nonquantal (non-vesicular) mechanism of secretion. Non-quantal release is continuous, independent on vagus activity and provides accumulation of ACh in myocardium in the presence of acetylcholinesterase (AChE) inhibitors. The aim of the present study was to determine the source of non-quantal ACh in isolated atrial myocardium of adult and newborn rats.
Main methods: Standard microelectrode technique was used to determine the cholinergic changes of electrical activity under the action of AChE inhibitor paraoxon, which correlates with the intensity of nonquantal ACh release.
Key findings: In adult rats selective inhibitor of neuronal choline uptake system hemicholinium III (10(-5) M) decreased all effects of paraoxon (5 × 10(-6) M) more than twofold. Inhibitor of polyspecific 3 organic cation transporters corticosterone (10(-4) M) also significantly decreased effects of paraoxon in adult rats, indicating that non-neuronal ACh, which is synthesized by cardiomyocytes, takes part in accumulation of ACh in the myocardium. When hemicholinium III and corticosterone were applied together, paraoxon effects in adult atrial myocardium were suppressed almost completely. In newborn rats cardiomyocytes do not excrete ACh. In accordance with this fact hemicholinium III completely abolished effects of paraoxon in newborn myocardium, while corticosterone was ineffective. Thus, non-quantal ACh is released both from cholinergic nerves and cardiomyocytes in adult rat myocardium, while it has exclusively neuronal nature in newborns.
Significance: The study demonstrates dual neuronal and non-neuronal nature of non-quantal ACh in the heart.