Aminoglycoside-induced blockade of reflex activity in the isolated spinal cord from the neonatal rat.
The subarachnoid injection of gentamicin into rats causes a transient flaccid paralysis of the hindlimbs lasting 1 to 5 hrs followed by a permanent flaccid paralysis which develops after 24 to 36 hrs. Although the early transient paralysis could be attributed to a pharmacologic blockade of central synaptic transmission, the mechanism of the blockade was not apparent. This study examines the effects of gentamicin and two other aminoglycoside antibiotics, kanamycin and neomycin, on reflex transmission in the isolated, hemisected spinal cord of the neonatal rat and the interaction with calcium. Gentamicin produced a concentration-dependent depression of reflex activity with a 50% inhibitory concentration of 1.6 mM at an external calcium concentration ([Ca2+]o) of 2.5 mM. Reducing the [Ca2+]o by half (i.e., to 1.25 mM) lowered the 50% inhibitory concentration of gentamicin to 0.22 mM. Gentamicin also increased the magnitude of homosynaptic depression of reflex activity in a manner qualitatively similar to that of decreasing [Ca2+]o. Lowering the [Ca2+]o potentiated the effect of gentamicin on homosynaptic depression. The actions of neomycin, kanamycin and magnesium on reflex transmission were nearly identical to those of gentamicin. These findings demonstrate that the early paralysis seen after subarachnoid injection of gentamicin may result from a central blockade of transmission. It is most likely that the site for blockade of reflex activity by gentamicin is presynaptic.
D000617:Aminoglycosides / Q000494:pharmacology*; D000818:Animals; D000831:Animals, Newborn / Q000502:physiology*; D002118:Calcium / Q000494:pharmacology; D004347:Drug Interactions; D005839:Gentamicins / Q000494:pharmacology; D066298:In Vitro Techniques; D008274:Magnesium / Q000494:pharmacology; D009407:Nerve Block; D051381:Rats; D011919:Rats, Inbred Strains; D012018:Reflex / Q000187:drug effects*; D013116:Spinal Cord / Q000187:drug effects*; D013569:Synapses / Q000187:drug effects
D000617:Aminoglycosides; D005839:Gentamicins; D008274:Magnesium; D002118:Calcium