Facilitation of acetylcholine release from cardiac parasympathetic nerve endings. Effect of stimulation pattern and Mn ions.

The influence of the stimulus intervals and the effect of Mn ions on facilitation of acetylcholine (ACh) release from parasympathetic nerve terminals were studied in quiescent guinea-pig auricles by electrophysiological methods. A maximum facilitation occurs at intervals of about 50ms. The half time of decay of facilitation after a conditioning stimulus is about 500ms. When conditioning trains of stimuli were applied, a second much longer lasting component of facilitation was found (t1/2 congruent to 4s). Mn ions, after exerting an inhibitory effect, cause an increase of ACh release, the development of which is dependent on frequent stimulation of the nerve fibres. This potentiation is accompanied by an apparent loss of facilitation. A further increase in ACh release occurs when superfusion is changed from Mn containing to normal Tyrode's solution. The decay to the control level displays a half time of about 20 min and can also be accelerated by frequent stimulation of the parasympathetic nerve fibres. It is suggested that Mn ions not only inhibit a Ca inward current but may also act on intracellular Ca2+ bindings sites in the nerve terminal. When these sites are blocked even a reduced Ca influx can be more effective in the process of transmitter release.