Linopirdine blocks α9α10-containing nicotinic cholinergic receptors of cochlear hair cells

María E. Gomez-Casati, Eleonora Katz, Elisabeth Glowatzki, María I. Lioudyno, Paul Fuchs, A. Belén Elgoyhen

Research output: Contribution to journalArticlepeer-review

Abstract

Studies of the electrophysiological response to acetylcholine (ACh) in mammalian outer hair cells (OHCs) are hindered by the presence of a large potassium current, IK,n, most likely mediated by channels containing the KCNQ4 subunit. Since IK,n can be blocked by linopirdine, cholinergic effects might be better revealed in the presence of this compound. The aim of the present work was to study the effects of linopirdine on the ACh-evoked responses through α9α10-containing native and recombinant nicotinic cholinergic receptors. Responses to ACh were blocked by linopirdine in both OHCs and inner hair cells (IHCs) of rats at postnatal days 21-27 (OHCs) and 9-11 (IHCs). In addition, linopirdine blocked responses of recombinant α9α10 nicotinic cholinergic receptors (nAChRs) in a concentration-dependent manner with an IC50 of 5.2 μM. Block by linopirdine was readily reversible, voltage independent, and surmountable at high concentrations of ACh, thus suggestive of a competitive type of interaction with the receptor. The present results contribute to the pharmacological characterization of α9α10-containing nicotinic receptors and indicate that linopirdine should be used with caution when analyzing the cholinergic sensitivity of cochlear hair cells.

Original languageEnglish (US)
Pages (from-to)261-269
Number of pages9
JournalJARO - Journal of the Association for Research in Otolaryngology
Volume5
Issue number3
DOIs
StatePublished - Sep 2004

Keywords

  • Acetylcholine
  • Ion channels
  • K channels
  • Linopirdine
  • Nicotinic receptors

ASJC Scopus subject areas

  • Otorhinolaryngology
  • Sensory Systems

Fingerprint Dive into the research topics of 'Linopirdine blocks α9α10-containing nicotinic cholinergic receptors of cochlear hair cells'. Together they form a unique fingerprint.

Cite this