6533b825fe1ef96bd12827fb

RESEARCH PRODUCT

Acetylcholine overflow during infusion of a high potassium-low sodium solution into the perfused chicken heart in the absence and presence of physostigmine.

subject

description

1. The effect of infusion of a modified Tyrode's solution (“high K+-low Na+ solution”) into the isolated chicken heart on the content of acetylcholine in the tissue and the overflow of acetylcholine were compared to those evoked by vagal stimulation. 2. The release of acetylcholine was measured over 15-min periods of either stimulation of the vagus nerves (40 V, 1 ms) at 20 Hz or of infusion of the high K+-low Na+ solution (108 mM K+, 44 mM Na+). 3. Both stimuli caused a maximum overflow of acetylcholine in the first few minutes whether or not 10−6 M physostigmine was present. The overflow was maintained during the vagal stimulation at a constant rate of at least 35% the initial rate, whereas the overflow evoked by the high K+-low Na+ solution ceased after 5 min. Under the latter conditions, the size of the acetylcholine store available for release (overflow in the presence of physostigmine) was 41% of the total store. 4. Physostigmine (10−6 M) caused a 2–3-fold increase of the overflow of acetylcholine evoked either by nerve stimulation or by infusion of the high K+-low Na+ solution. Reduction of [Ca2+]o from 1.8 to 0.2 mM strongly reduced the overflow caused by either kind of stimulation. 5. The sum of the overflow evoked by the high K+-low Na+ solution and the cardiac content of acetylcholine after the stimulation did not exceed the cardiac content before stimulation. 6. In conclusion, infusion of a high K+-low Na+ solution caused an overflow of acetylcholine in the absence and presence of physostigmine that was similar to that evoked by nerve stimulation with respect to Ca2+-dependency and hydrolysis of the released acetylcholine. The rate of synthesis of acetylcholine maintaining a steady state release was high during nerve stimulation, but was blocked during infusion of the high K+-low Na+ solution, presumably by block of the high affinity uptake of choline.