Block of the α9 nicotinic receptor by ototoxic aminoglycosides

Carla V. Rothlin, Eleonora Katz, Miguel Verbitsky, Douglas E. Vetter, Stephen F. Heinemann, A. Belén Elgoyhen

Research output: Contribution to journalArticlepeer-review

26 Scopus citations


In the present study, we report that the α9 nicotinic acetylcholine receptor (nAChR) expressed in Xenopus laevis oocytes is reversibly blocked by aminoglycoside antibiotics. The aminoglycosides tested blocked the α9 nAChR in a concentration-dependent manner with the following rank order of potency: neomycin>gentamicin>streptomycin>amikacin>kanamycin. The antagonistic effect of gentamicin was not overcome by increasing the concentration of acetylcholine (ACh), indicative of a non-competitive type of block. Blockage of ACh-evoked currents by gentamicin was found to be voltage-dependent, being more potent at hyperpolarized than at depolarized holding potentials. Furthermore, gentamicin blockage was dependent upon the extracellular Ca2+ concentration, shown by the fact that increments in extracellular Ca2+ significantly reduced the potency of this aminoglycoside to block the α9 nAChR. Possible mechanisms of blockage by the aminoglycosides are discussed. The present results suggest that the initial reversible actions of aminoglycosides at the organ of Corti, such as the elimination of the olivocochlear efferent function, are due in part to the interaction with the native α9-containing cholinergic receptor of the outer hair cells. Copyright (C) 2000 Elsevier Science Ltd.

Original languageEnglish (US)
Pages (from-to)2525-2532
Number of pages8
Issue number13
StatePublished - 2000
Externally publishedYes


  • Aminoglycosides
  • Hair cells
  • Nicotinic receptors
  • Ototoxicity

ASJC Scopus subject areas

  • Cellular and Molecular Neuroscience
  • Drug Discovery
  • Pharmacology


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