Non-quantal release of acetylcholine from parasympathetic nerve terminals in the right atrium of rats.
Acetylcholinesterase (AChE) inhibitors provoke typical cholinergic effects in the isolated right atrium of the rat due to the accumulation of acetylcholine (ACh). Our study was designed to show that in the absence of vagal impulse activity, ACh is released from the parasympathetic nerve fibres by means of non-quantal secretion. The conventional microelectrode technique was used to study changes in action potential (AP) configuration in the right atrium preparation of rats during application of AChE inhibitors. Staining with the lipophilic fluorescent dye FM1-43 was used to demonstrate the presence of endocytosis in cholinergic endings. The AChE inhibitors armin (10(7)-10(5)m) and neostigmine (10(7) to 5 x 10(6)m) caused a reduction of AP duration and prolonged the cycle length. These effects were abolished by atropine and were therefore mediated by ACh accumulated in the myocardium during AChE inhibition. Putative block of impulse activity of the postganglionic neurons by tetrodotoxin (5 x 10(7)m) and blockade of ganglionic transmission by hexomethonium (2 x 10(4)m), as well as blockade of all forms of quantal release with Clostridium botulinum type A toxin (50 U ml(1)), did not alter the effects of armin. Experiments with FM1-43 dye confirmed the effective block of exocytosis by botulinum toxin. Selective inhibition of the choline uptake system using hemicholinium III (10(5)m), which blocks non-quantal release at the neuromuscular junction, suppressed the effects of AChE inhibitors. Thus, accumulation of ACh is likely to be caused by non-quantal release from cholinergic terminals. We propose that non-quantal release of ACh, shown previously at the neuromuscular junction, is present in cholinergic postganglionic fibres of the rat heart in addition to quantal release.
Abramochkin
Denis V
DV
Department of Human and Animal Physiology, Biological Faculty of the Moscow State University, Leninskije Gory, 1, 12, Moscow, Russia. abram340@mail.ru
Nurullin
Leniz F
LF
Borodinova
Anastasia A
AA
Tarasova
Nadezhda V
NV
Sukhova
Galina S
GS
Nikolsky
Eugen E
EE
Rosenshtraukh
Leonid V
LV
D000109:Acetylcholine / Q000378:metabolism*; D000818:Animals; D006325:Heart Atria / Q000294:innervation* / Q000378:metabolism*; D018377:Neurotransmitter Agents / Q000378:metabolism*; D010275:Parasympathetic Nervous System / Q000378:metabolism*; D017729:Presynaptic Terminals / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D009435:Synaptic Transmission / Q000502:physiology*
D018377:Neurotransmitter Agents; D000109:Acetylcholine