Electrophysiological phenotype of auditory hair cells in alpha10 knockout mice

BALLESTERO J; GOMEZ CASATI ME; TARANDA J; LIPOVSEK M; SAVINO J; VETTER D; BOULTER J; ELGOYHEN AB; KATZ E

Buenos Aires

Congreso; XXII Congreso latinoamericano y 1ero iberoamericano de ciencias fisiológicas; 2006

Electrophysiological phenotype of auditory hair cells in a10 knockout mice. Jimena Ballestero1, María Eugenia Gómez-Casati1, Julián Taranda1, Marcela Lipovsek1, Jessica Savino1, Douglas Vetter2, Jim Boulter3, Belén Elgoyhen1, Eleonora Katz1 1 INGEBI-CONICET, UBA, Argentina; 2 Tufts Univ. USA; 3 UCLA, USA. In the Organ of Corti, the sensory epithelia of the of the auditory system, hair cells transduce sound stimuli into electrical signals. Hair cell function is modulated by efferent cholinergic olivocochlear (OC) fibers. This synapse is inhibitory and mediated by the a9a10 nicotinic receptor and the subsequent activation of Ca2+-activated K+ channels (SK). We have recently generated an a10 ‘knockout’ mouse to assess the role of the a10 gene in the development and function of the OC system. Functional studies performed on this animal showed that stimulation of OC fibers produces an enhancement of OHC function rather than the suppression or the lack of response observed in wildtype and a9 ‘knockout’ mice, respectively. We evaluated the presence of cholinergic currents in inner hair cells (IHCs) at postnatal ages (P) P8-P9 and in outer hair cells (OHCs) at P10-P12 and also characterized their voltage-gated currents during development. Whole cell recordings were performed in hair cells of a10 ‘knockout’(-/-) mice and their heterozygous(+/-) and wildtype(+/+) littermates. We found no evidence of acetylcholine (ACh)-evoked currents in IHCs of (-/-) mice whereas small currents were detected in ~50% of OHCs. Neither OHCs nor IHCs from (-/-) mice presented K+-induced synaptic currents. In contrast, (+/-) and (+/+) mice showed robust ACh-evoked currents and K+-induced synaptic activity. No differences were found in the amplitude, voltage sensitivity, reversal potential and activation kinetics of K+-currents in IHCs from (-/-) mice. The presence of cholinergic currents in OHCs of a10 (-/-) mice suggests that the a9 subunit could be functioning as an homomeric receptor in these cells. The lack of the a10 subunit together with the activity of a9 homomeric receptors poorly or not coupled to SK channels could explain the anomalous behavior of the OC system.