Decrease in calcium currents induced by aminoglycoside antibiotics in frog motor nerve endings.
1. The effects of the aminoglycoside antibiotics, streptomycin, neomycin and gentamicin were examined on perineural currents and evoked acetylcholine (ACh) release at frog motor nerve endings. 2. In the standard solutions used previously to measure Ca2+ currents, streptomycin reduced the peak amplitude of the Ca2+ component of the perineural current. 3. In a solution in which changes in both Ca2+ currents and evoked ACh release can be recorded simultaneously, both Ca2+ currents and evoked ACh release were reduced by aminoglycosides in the potency order neomycin > streptomycin > gentamicin. This potency sequence is similar to that reported previously for these agents as inhibitors of neurally-evoked contractions of mammalian skeletal muscle. 4. These data suggest that the presynaptic inhibitory effects of aminoglycoside antibiotics at the neuromuscular junction occur as a consequence of a reduction in Ca2+ currents in the motor nerve terminal.
Department of Molecular Pharmacology and Biological Chemistry, Northwestern University Medical School, Chicago, IL 60611.
R S
RS
Redman
E M
EM
Silinsky
D000109:Acetylcholine / Q000378:metabolism; D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D004594:Electrophysiology; D005839:Gentamicins / Q000494:pharmacology; D066298:In Vitro Techniques; D009046:Motor Neurons / Q000187:drug effects / Q000378:metabolism*; D018482:Muscle, Skeletal / Q000187:drug effects / Q000294:innervation / Q000378:metabolism; D009355:Neomycin / Q000494:pharmacology; D009411:Nerve Endings / Q000187:drug effects / Q000378:metabolism*; D011898:Ranidae; D013307:Streptomycin / Q000494:pharmacology; D014403:Tubocurarine / Q000494:pharmacology
D000900:Anti-Bacterial Agents; D002121:Calcium Channel Blockers; D005839:Gentamicins; D009355:Neomycin; D000109:Acetylcholine; D014403:Tubocurarine; D013307:Streptomycin