The effects of the antibiotic, primycin, on spontaneous transmitter release at the neuromuscular junction

The effects of primycin, a potent ionophore in biological membranes, have been studied at the neuromuscular junction of the garter snake. Primycin in concentrations greater than 2 X 10(-7)M produced a time- and concentration-dependent depolarization of twitch muscle fibres. Primycin (10(-7)-5 X 10(-7)M) produced an increased rate of quantal release of acetylcholine, which was not maintained, and a slight reduction in quantal size. Time to onset and to peak effect of primycin were concentration-dependent whereas maximum frequency was not. Absence of extracellular Ca2+ produced a significant delay in the time to onset and to peak effect of primycin, but did not affect the peak miniature endplate potential (m.e.p.p.) frequency. Following 60 min exposure to primycin (5 X 10(-7)M), introduction of a high concentration of potassium (20 mM) produced no further increase in spontaneous release. In cut muscle preparations, exposure to primycin (10(-7)-5 X 10(-7)M) reduced peak endplate current (e.p.c.) amplitude until nerve stimulation resulted in failures or the release of one or two quanta. E.p.c. amplitude was not restored with prolonged washing. The effects of primycin on the nerve terminal are considered to be consistent with its ability to increase the permeability of membranes to calcium ions resulting in an influx of extracellular calcium, an efflux of mitochondrial calcium and eventual depletion of synaptic vesicles.