title: Effects of the antibiotic gentamicin on nicotinic acetylcholine receptors.
abstract: 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 alphabetagammadelta-AChR and neuronal alpha9-AChR. We studied the effects of gentamicin on heteromeric alphabetagammadelta-AChR and homomeric alpha7-AChR expressed in Xenopus oocytes. Prolonged treatment with gentamicin, and other antibiotics, differentially altered alphabetagammadelta- and alpha7-AChR responses. Specifically, gentamicin accelerated desensitization and did not reduce ACh-currents in oocytes expressing alphabetagammadelta-AChRs, whereas ACh-currents were reduced and desensitization was unaltered in oocytes expressing alpha7-AChRs. Moreover, acutely applied gentamicin acted as a competitive antagonist on both types of receptors and increased the rate of desensitization in alphabetagammadelta-AChR while reducing the rate of desensitization in alpha7-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.
authors.affiliation: Laboratory of Cellular and Molecular Neurobiology, Department of Neurobiology and Behavior, University of California, Irvine, CA 92697-4550, USA. mascia.amici@uniroma1.it
authors.forename: Mascia
authors.initials: M
authors.lastname: Amici
authors.forename: Fabrizio
authors.initials: F
authors.lastname: Eusebi
authors.forename: Ricardo
authors.initials: R
authors.lastname: Miledi
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D003051:Cochlea / Q000187:drug effects; D018076:DNA, Complementary / Q000096:biosynthesis; D004594:Electrophysiology; D005839:Gentamicins / Q000494:pharmacology*; D006801:Humans; D066298:In Vitro Techniques; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D051379:Mice; D018733:Nicotinic Antagonists; D009865:Oocytes / Q000378:metabolism; D018408:Patch-Clamp Techniques; D018075:RNA, Complementary / Q000096:biosynthesis; D011978:Receptors, Nicotinic / Q000096:biosynthesis / Q000187:drug effects* / Q000235:genetics; D014101:Torpedo; D014722:Vestibule, Labyrinth / Q000187:drug effects; D014981:Xenopus; D064569:alpha7 Nicotinic Acetylcholine Receptor
chemical_list: D000900:Anti-Bacterial Agents; C579167:Chrna7 protein, human; C579166:Chrna7 protein, mouse; D018076:DNA, Complementary; D005839:Gentamicins; D018733:Nicotinic Antagonists; D018075:RNA, Complementary; D011978:Receptors, Nicotinic; D064569:alpha7 Nicotinic Acetylcholine Receptor