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 alpha beta gamma delta-AChR and neuronal alpha 9-AChR. We studied the effects of gentamicin on heteromeric alpha beta gamma delta-AChR and homomeric alpha 7-AChR expressed in Xenopus oocytes. Prolonged treatment with gentamicin, and other antibiotics, differentially altered alpha beta gamma delta- and alpha 7-AChR responses. Specifically, gentamicin accelerated desensitization and did not reduce ACh-currents in oocytes expressing alpha beta gamma delta-AChRs, whereas ACh-currents were reduced and desensitization was unaltered in oocytes expressing alpha 7-AChRs. Moreover, acutely applied gentamicin acted as a competitive antagonist on both types of receptors and increased the rate of desensitization in alpha beta gamma delta-AChR while reducing the rate of desensitization in alpha 7-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. (c) 2005 Elsevier Ltd. All rights reserved.