Ca2+ modulates nicotinic ACh receptors of inner hair cells in the neonatal rat cochlea.

GÓMEZ-CASATI, ME; FUCHS PA; ELGOYHEN, AB; KATZ E

Daytona Beach, FL, USA

Congreso; The Association for Research in Otolaryngology, midwinter meeting; 2004

In the neonatal mammalian cochlea, inner hair cells (IHCs) are transiently innervated by efferent fibers of the olivocochlear (OC) system. This synapse is inhibitory and mediated by a nicotinic acetylcholine receptor (nAChR) (Glowatzki & Fuchs 2000). Electrophysiological and pharmacological data support the hypothesis that inhibition is brought about by Ca2+ flowing in through the alpha9alpha10-containing nAChR and the subsequent activation of an apamin sensitive Ca2+-dependent K+ (SK) channel.The functional properties of native nAChRs were studied using whole-cell recordings of IHCs in excised apical turns of the rat organ of Corti (P8-11). To isolate nAChR currents from SK channel currents, experiments were performed with 10 mM BAPTA in the pipette solution and 1 nM apamin in the external solution.We examined the effects of Ca2+ on cation currents through the IHC nAChR. ACh-evoked currents were potentiated by low Ca2+ concentrations (up to 0.5 mM) and were blocked by higher concentrations of this cation. Concentration-response curves show that the receptor had an apparent affinity for ACh of 60.7 uM in a saline containing 0.5 mM Ca2+. In the absence of Ca2+, the EC50 for ACh increased, suggesting that potentiation by Ca2+ involves changes in the apparent affinity of the receptor for ACh. In addition to these effects of Ca2+, ACh-evoked responses were reduced during continuous application of 1 mM ACh. At a holding potential of –90 mV, the current remaining after 20 sec was 54.2% of its peak value. These biophysical characteristics of the IHC nAChR closely resemble those of the recombinant alpha9alpha10 nAChR (Elgoyhen et al., 2001, Weisstaub et al., 2002), reinforcing the hypothesis that the nAChR at the OC-IHC synapse is composed of both alpha9 and alpha10 subunits.