The variation of acetylcholine release from myenteric neurones with stimulation frequency and train length

Summary

• 1. The effects of scopolamine on the release of ³H-acetylcholine (ACh) from the guinea-pig myenteric plexus were studied at different stimulation frequencies (0.03–10 Hz) and train lengths (1–180 pulses). Release of ³H-ACh was measured in the absence of cholinesterase inhibitors as the outflow of tritium from myenteric plexus-longitudinal muscle preparations preloaded with ³H-choline.

• 2. In control experiments the volley output of ³H-ACh declined with increasing train length and increasing stimulation frequency. Stimulation by one pulse produced the highest volley output.

• 3. Scopolamine facilitated the evoked output of ³H-ACh via blockade of presynaptic muscarine receptors. A significant increase was already observed when the preparation was stimulated with 3 pulses at 10 Hz which indicates that the inhibitory muscarinic mechanism becomes operational within 200 ms. The facilitatory effects of scopolamine depended on both train length and frequency of stimulation. Maximal increases in ³H-ACh output were seen with brief trains (3 and 6 pulses) at a high frequency (10 Hz), or with longer trains (20 and 180 pulses) at lower frequencies (0.3 and 1 Hz).

• 4. Scopolamine compensated for the frequencydependent decline of ³H-ACh volley output only during brief periods of stimulation (3 and 6 pulses). It is therefore concluded that the decline in volley output during the first few pulses of a train is due to the negative feedback mechanism which is activated by the transmitter released by the preceding impulses. With longer trains of stimulation the negative feedback mechanism plays only a minor role in regulating the output per pulse.