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Non‐quantal release of acetylcholine in rat atrial myocardium is inhibited by noradrenaline
Author(s) -
Borodinova Anastasia A.,
Abramochkin Denis V.,
Sukhova Galina S.
Publication year - 2013
Publication title -
experimental physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.925
H-Index - 101
eISSN - 1469-445X
pISSN - 0958-0670
DOI - 10.1113/expphysiol.2013.074989
Subject(s) - acetylcholine , cholinergic , chemistry , neurotransmitter , adrenergic , medicine , acetylcholinesterase , endocrinology , exocytosis , paraoxon , stimulation , secretion , biology , biochemistry , receptor , enzyme
New findings• What is the central question of this study? Is non‐quantal release of ACh in the heart regulated by noradrenaline or does it represent uncontrolled leakage of ACh from cardiac cholinergic fibres? • What is the main finding and its importance? Cardiac non‐quantal ACh release can be negatively regulated by noradrenaline. This finding suggests that non‐quantal release has physiological relevance and is also important in the context of cholinergic–adrenergic interactions in the heart.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 × 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 α‐adrenoceptors, because all experiments were conducted in the presence of the β‐blocker propranolol (5 × 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 α 2 ‐antagonist yohimbine (10 −6 m ). However, both the α 1 ‐agonist phenylephrine (10 −6 m ) and the α 2 ‐agonist clonidine (10 −6 m ) significantly inhibited the cholinergic effects of paraoxon, indicating the possible involvement of both α‐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.