Expression of voltage-gated currents in cohlear inner hair cells of nAChR alpha10 "knockout" mice during development

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

Baltimore, USA

Congreso; 29th Midwinter Meeting, Association for Research in Otolaryngology; 2006

Cochlear inner hair cells (IHC) release neurotransmitter onto afferent auditory nerve fibers in response to sound stimulation. During early development, synaptic transmission is triggered by spontaneous Ca2+ spikes, which are modulated by an efferent cholinergic innervation to IHCs. This synapse is inhibitory and mediated by the a9a10 nAChR. After the onset of hearing, large-conductance Ca2+-activated K+ channels are acquired and both spontaneous action potentials and the efferent innervation disappear from IHCs. We are studying the developmental changes in membrane properties in cochlear IHC of nAChR a10 ‘knockout’ mice in order to evaluate whether there are changes in the functional expression pattern of the different channels during development due to the lack of the a10 subunit.  Electrophysiological properties of IHCs were studied by whole cell recordings in acutely excised apical turns of the organ of Corti. Before the onset of hearing, IHCs from wild type and heterozygous mice have slow voltage responses and fire spontaneous action potentials. Preliminary experiments in IHCs from a10 knockout mice, show there are no changes in the peak amplitude (3909 ± 722 pA [+/+], 3468 ± 404 pA [+/-] and 2923 ± 642 pA [-/-]), voltage sensitivity and reversal potential (–64 ± 6.5 mV [+/+], -67 ± 1.8 mV [+/-] and –72 ± 5.1 mV [-/-]) of the total K+-currents after the onset of hearing with respect to their wild-type and heterozygous littermates. Moreover, outward currents have the additional fast component (t, 0.23 ± 0.06 ms at 46 mV) indicative of a functional BK channel as previously documented (Kros et al., 1998). We are now evaluating whether there are changes in the expression and kinetics of Ca2+ and K+ channels before the onset of hearing and their impact on spontaneous action potentials.