Effects of the antibiotic gentamicin on nicotinic acetylcholine receptors

Medical treatment with the aminoglycosidic antibiotic gentamicin may produce side effects that include neuromuscular blockage and ototoxicity; which are believed to result from a dysfunction of nicotinic acetylcholine receptors (AChRs). Gentamicin is known to reversibly block ACh-currents generated by the activation of muscle-type αβγδ-AChR and neuronal α9-AChR. We studied the effects of gentamicin on heteromeric αβγδ-AChR and homomeric α7-AChR expressed in Xenopus oocytes. Prolonged treatment with gentamicin, and other antibiotics, differentially altered αβγδ- and α7-AChR responses. Specifically, gentamicin accelerated desensitization and did not reduce ACh-currents in oocytes expressing αβγδ-AChRs, whereas ACh-currents were reduced and desensitization was unaltered in oocytes expressing α7-AChRs. Moreover, acutely applied gentamicin acted as a competitive antagonist on both types of receptors and increased the rate of desensitization in αβγδ-AChR while reducing the rate of desensitization in α7-AChR. This data helps to better understand the action of gentamicin on muscle and nervous tissues, providing mechanistic insights that could eventually lead to improving the medical use of aminoglycosides.