Calcium antagonism and reversibility of gentamicin-induced loss of cochlear microphonics in the guinea pig.
The perilymphatic space of the guinea pig cochlea was perfused with various concentrations of Ca2+, Mg2+ and gentamicin. Cochlear microphonic potentials (CM) were essentially stable when solutions contained 1 mM Ca2+ plus 2 mM Mg2+, 1 mM Ca2+ and no Mg2+ or when both Ca2+ and Mg2+ were omitted. In the absence of Ca2+, the presence of 2 mM Mg2+ or 1 mM EGTA markedly decreased CM. Addition of 3 mM gentamicin lowered CM, the magnitude of the effect depending on the concentration of Ca2+ present. Ten mM Ca2+ eliminated the action of the drug. In the absence of Ca2+, the effects of Mg2+ and gentamicin were additive. When the application of gentamicin was followed by perfusion with drug-free medium, suppression of CM by 3 mM drug could be reversed with 10 mM Ca2+ but not with 1 mM Ca2+. Loss of CM was irreversible when administration of 10 mM Ca2+ was delayed or when the drug concentration was increased to 10 mM. The results are consistent with our previous hypothesis of a biphasic mechanism of aminoglycoside toxicity: an initial action competitive with calcium ions and reversible and a second step, non-competitive and irreversible.
D000617:Aminoglycosides / Q000009:adverse effects / Q000037:antagonists & inhibitors; D000818:Animals; D002118:Calcium / Q000008:administration & dosage / Q000494:pharmacology*; D002121:Calcium Channel Blockers; D003051:Cochlea / Q000187:drug effects; D003055:Cochlear Microphonic Potentials / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D005072:Evoked Potentials, Auditory / Q000187:drug effects*; D005839:Gentamicins / Q000009:adverse effects* / Q000037:antagonists & inhibitors; D006168:Guinea Pigs; D008274:Magnesium / Q000494:pharmacology; D008297:Male; D013997:Time Factors
D000617:Aminoglycosides; D002121:Calcium Channel Blockers; D005839:Gentamicins; D008274:Magnesium; D002118:Calcium