THE ROLE OF NONQUANTAL RELEASE OF ACETYLCHOLINE IN REGULATION OF POSTSYNAPTIC MEMBRANE ELECTROGENESIS

In mammalian nerve-muscle preparations treated with an anticholinester ase, the acetylcholine (ACh) released non-quantally (NQR) reaches the postsynaptic receptors and causes a small depolarization of the membra ne potential at the endplate region of the muscle fibres. Increase in quantal release potentiates the NQR and vice versa, the amplitude and the kinetic parameters of quantal miniature endplate currents (MEPCs) change during manipulation of NQR, indicating direct interaction betwe en both types of release. Repetitive binding of ACh to postsynaptic re ceptors which prolongs the lime course of MEPCs in anti-cholinesterase -treated endplates leads within 1-2 h to progressive desensitization i n the presence of non-quantal release and to the subsequent shortening of the quantal responses, We have also investigated the effect of pro cedures known to modulate non-quantal acetylcholine release, on the sm all, but obvious, difference in the resting membrane potential between tile endplate zone and other areas of the mouse muscle fibre. The res ting membrane potential at the endplate zone with intact cholinesteras e is more negative (by 2-4 mV) than in the endplate-free area. The exp eriments were performed to rest the hypothesis that the hyperpolarizat ion is caused by an electrogenic Na+-K+ pump operating during the acti on of ACh released in non-quantal form. Observations in favour of this idea are that both short-term denervation (which eliminates non-quant al but not quantal release) and ouabain abolish the local synaptic hyp erpolarization and that subsequent application of low doses of ACh res tores it. It follows, therefore, that the hyperpolarization is probabl y caused by a small but continuous ACh leakage from the nerve terminal .