“Linopirdine blocks a9a10-containing nicotinic cholinergic receptors of cochlear hair cells

GOMEZ CASATI ME; KATZ E; GLOWATZKI E; LIOUDYNO ML; FUCHS P; ELGOYHEN AB

J Assoc for Research in Otolaryngology

Año: 2004 vol. 5 p. 261 - 265

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 determine if linopirdine has a direct effect on the ACh-evoked responses through a9a10-containing native and recombinant nicotinic cholinergic receptors. Responses to 100 mM ACh were blocked by linopirdine both in OHCs and inner hair cells (IHCs). In addition, linopirdine blocked responses of recombinant a9a10 nicotinic cholinergic receptors (nAChRs) in a concentration-dependent manner with an IC50 of  5.2 mM. 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 indicate that linopirdine should be used with caution when analyzing the cholinergic sensitivity of cochlear hair cells