Competitive antagonism between calcium and antibiotics at the neuromuscular junction.

The neuromuscular blockade produced by the amino-glycosidic-aminocyclitolic antibiotics streptomycin and kanamycin and its reversal by calcium was quantitatively studied in the isolated phrenic nerve-diaphragm preparation of the rat. The low dose-response curves obtained presenting no significant deviation from parallelism are highly suggestive of a competitive type of antagonism between those substances. The streptidinic moiety of streptomycin showed the same properties as the original antibiotic. Streptomycin and kanamycin decreased the amplitude of intracellularly recorded e.p.p.'s of the toad sartorius muscle in a manner quite similar to that described for magnesium ions which suggests an interference of the antibiotics with the cooperative interaction of calcium ions with specific receptive sites at the presynaptic membrane of the neuromuscular junction.