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

Abstract

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 × 10−7m produced a time‐ and concentration‐dependent depolarization of twitch muscle fibres. Primycin (10−7‐5 × 10−7m) 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 × 10−7m), 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 × 10−7m) 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.

In vitro interactions between primycin and different statins in their effects against some clinically important fungi

“…The antimicrobial action of PN is thought to be due to an increase in the ionic permeability of the cell membrane (Horvath et al, 1979). PN may act as an ionophore in many membrane systems; it can cause changes in the membrane potentials of liver mitochondrial inner membranes (Meszaros et al, 1980), and it also has effects on transmitter release at the neuromuscular junctions (Henderson & Marshall, 1984). Due to its toxicity in animal models, PN is limited to topical use in the treatment of skin infections (Vályi-Nagy et al, 1954).…”