In the mammalian myocardium, ACh, which is the main neurotransmitter of cardiac parasympathetic postganglionic fibres, can be released via both quantal (vesicular) and non-quantal (non-vesicular) mechanisms of secretion. Non-quantal release is continuous and independent of vagus activity and exocytosis of ACh-containing vesicles. During the incubation of myocardium in the presence of acetylcholinesterase (AChE) inhibitors, non-quantal ACh release leads to accumulation of ACh in the myocardium and cholinergic effects, which are proportional to the intensity of non-quantal secretion. The aim of the present study was to reveal whether non-quantal release of ACh can be modulated by another major cardioregulator, noradrenaline, or whether it represents uncontrolled leakage of ACh from cholinergic fibres. Cholinergic changes of electrical activity induced by the AChE inhibitor paraoxon (5 x 10(-6) m) in isolated rat right atrial preparations were determined by means of a standard microlectrode technique and used as a measure of the intensity of non-quantal release. Noradrenaline (10(-7) and 10(-6) m) substantially suppressed, but did not abolish, effects of paraoxon via stimulation of alpha-adrenoceptors, because all experiments were conducted in the presence of the beta-blocker propranolol (5 x 10(-6) m). A blocker of ganglionic transmission, hexamethonium bromide (10(-4) m), failed to alter the inhibitory effect of noradrenaline, indicating that only non-quantal ACh release is suppressed by this neurotransmitter. The effects of noradrenaline could be reduced by the alpha2-antagonist yohimbine (10(-6) m). However, both the alpha1-agonist phenylephrine (10(-6) m) and the alpha2-agonist clonidine (10(-6) m) significantly inhibited the cholinergic effects of paraoxon, indicating the possible involvement of both alpha-adrenoceptor subtypes in mediation of the adrenergic inhibition of non-quantal ACh release. Thus, cardiac non-quantal ACh release can be negatively regulated by noradrenaline, providing another facet of sympathetic-parasympathetic interaction in the heart.
        
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Borodinova AA, Abramochkin DV, Sukhova GS (2013) Non-quantal release of acetylcholine in rat atrial myocardium is inhibited by noradrenaline Exp Physiol98: 1659-67