6533b873fe1ef96bd12d56db

RESEARCH PRODUCT

The role of choline in the release of acetylcholine in isolated hearts.

subject

description

1. The concentrations of acetylcholine, choline and noradrenaline were estimated in the perfusate (overflow) of isolated hearts of chickens, cats, rabbits and guinea pigs. Neurotransmitter release was evoked by stimulation of both vagus nerves and by direct stimulation of the heart (field stimulation). 2. In the absence of exogenous choline and physostigmine, field stimulation at 20 Hz for 20 min caused an overflow of acetylcholine from the hearts of the 4 species investigated. During vagal stimulation, however, acetylcholine was detected only in the perfusate of the chicken heart. 3. Field stimulation for 2 min caused an overflow of 193 pmol g−1 min−1 acetylcholine and of 666 pmol g−1 min−1 noradrenaline from the guinea pig heart; pretreatment of the animals with reserpine blocked the release of noradrenaline but left the overflow of acetylcholine unaltered. 4. When the overflow of acetylcholine was evoked by vagal stimulation, infusion of 10−5 M choline into the cat and chicken heart caused an increase in the overflow that was 2–3-fold in the chicken heart and at least 23-fold in the cat heart (23 times the limit of estimation). In the presence of choline, the overflow of acetylcholine from the hearts of the 4 species evoked by field stimulation was 2–3 times the overflow in the absence of the drug. 5. Inhibition of the cholinesterase activity by 10−6 M physostigmine raised the overflow of acetylcholine evoked by vagal and/or by field stimulation uniformly by a factor of 2 to 3 in the 4 species investigated. In the cat heart, the combination of 10−5 M choline and 10−6 M physostigmine increased the overflow evoked by field stimulation for 20 min from 0.54 to 3.6 nmol g−1 20 min−1, i.e. by a factor of 7. 6. The cardiac content of acetylcholine was highest in the chicken heart (9.8 nmol/g) and lowest in the guinea pig heart (2.1 nmol/g). 7. The spontaneous efflux of choline from the isolated hearts after 15 min of perfusion ranged from 0.4 (cat) to 2.1 nmol g−1 min−1 (chicken) and was maintained at these levels for at least 1 h. 8. In the blood of chickens, cats and rabbits, the choline concentration was 0.5–1.0×10−5 M. 9. It is concluded that (1) an appreciable amount of acetylcholine released from parasympathetic nerves escapes into the circulation of isolated hearts, (2) the extent of the extracellular hydrolysis of acetylcholine is the same in avian and mammalian hearts, (3) the release of acetylcholine evoked by vagal stimulation is much smaller in the isolated cat heart than that in the chicken heart, because of an insufficient ganglionic transmission due to a deficiency in extracellular choline and finally (4) the amount of acetylcholine released by vagal stimulation is dependent on both the efflux of choline from extraneuronal sources and the overall density of the cholinergic innervation of the heart.