EFFECTS OF THE AMINOGLYCOSIDE ANTIBIOTICS, STREPTOMYCIN AND NEOMYCIN, ON NEUROMUSCULAR-TRANSMISSION .1. PRE-SYNAPTIC CONSIDERATIONS

Abstract

The effects of 2 aminoglycoside antibiotics, streptomycin and neomycin, were studied in voltage-clamped transected twitch fibers of the costocutaneous muscles of garter snakes (species Thamnophis). The concentration-dependent effects of each antibiotic were quantitated by measuring miniature end-plate currents (mepc) and evoked end-plate currents (epc) in a single fiber before and in the presence of a wide range of concentrations of each antibiotic. The amplitude and the kinetics of these currents were studied and estimates of the quantal content of evoked transmitter release determined by the direct method of mean ratios, .**GRAPHIC**. a distinct separation was obtained between the concentrations of each antibiotic which demonstrated either pre- or postsynaptic actions. Both streptomycin and neomycin produced a concentration-dependent reduction in epc amplitude at concentrations which did not reduce mepc amplitude. The primary site of action for these antibiotics was considered of presynaptic origin. Streptomycin was .apprx. 1/10 as active as neomycin in reducing quantal release of acetylcholine. The marked depression in epc amplitude and quantal content produced by high concentrations of each antibiotic were reversed by elevating the external Ca concentration. Double logarithmic plots of the relationshp between external Ca concentration and epc amplitude yielded a slope of .apprx. 3.8 in control physiological solution. In the presence of blocking concentrations of each antibiotic, increasing the external Ca concentration caused a parallel shift to the right of this relationship. The major mechanism for the neuromuscular depression produced by these aminoglycoside antibiotics is apparently a competitive antagonism with Ca for a common presynaptic site required for evoked transmitter release.