Effects of lithium on the spontaneous quantal release of transmitter from motor terminals of the diaphragm of rats

The mean miniature endplate potentials (m.e.p.p.) frequency has been examined at the neuromuscular junctions of the rat diaphragm, at 20 degrees and 37 degrees C, when all or part of the NaCl of the Krebs solution was replaced by LiCl. A high level of substitution (100% and 75%) causes initially an increase in m.e.p.p. frequency. This initial process can be fitted by an exponential function of time with a time constant which decreases with Li+ concentration and temperature. After reaching a maximum, m.e.p.p. frequency returns to a lower steady level which is higher than the one observed before the substitution and rises when either Li+-concentration or temperature are increased. At 37 degrees C, when the substitution of Li for Na+ is lower than 50%, m.e.p.p. frequency progressively rises towards a steady value which can be maintained for a long period. At 37 degrees C, a significant rise in m.e.p.p. frequency can be observed even after the replacement of 10% NaCl by LiCl. In the presence of prostigmine, m.e.p.p. disappear from the rat neuromuscular junction treated by Li, following an exponential decrease in frequency. These results are discussed in terms of presynaptic site of action of Li+. It is proposed that choline re-uptake by the presynaptic terminals could be sufficient to maintain a flow of acetylcholine release even after a complete substitution of LiCl for NaCl.