The cholinergic response of cochlear inner hair cells is correlated with expression of the alpha10 nicotinic subunit

GÓMEZ-CASATI ME; ELGOYHEN, AB

Costa Rica

Congreso; Pew annual meeting; 2005

In the mature cochlea, inner hair cells (IHCs) transduce acoustic signals into receptor potentials, communicating to the brain by synaptic contacts with afferent fibers. Before the onset of hearing, about postnatal day 11 in rats, a transient efferent innervation is found on IHCs. Evoked synaptic release from efferent neurons could modulate the firing frequency of IHCs and play a role in the establishment of the adult innervation to the cochlea. This efferent synapse is inhibitory and mediated by a nicotinic cholinergic receptor probably formed by the alpha9 and alpha10 subunits. Expression of alpha9 mRNA persists in adult rat IHCs, while that of alpha10 does not. We have characterized cholinergic input to IHCs during this developmental transition. We used whole cell recordings of IHCs in acutely excised apical turns of the rat organ of Corti. At a holding potential of –90 mV, ACh elicited inward currents (-449 +/- 74 pA) in 8 of 8 IHCs at P7-9 and 5 of 5 cells exhibited efferent synaptic currents upon K+ depolarization. At P10-12, ACh elicited currents of –264 +/- 43 pA (16 of 16) and 14 of 15 IHCs had efferent synaptic currents. At P13-14, ACh elicited currents of smaller amplitude (-29 +/- 5 pA) in 3 of 5 IHCs and efferent synaptic currents appeared in 2 of 4 cells. By P18, only 1 of 6 IHCs responded to ACh and 0 of 10 cells tested had efferent synaptic currents. In situ hybridization showed alpha10 expression in IHCs at P3. Expression decreased at P13, and by P21 was undetectable. The correlation of cholinergic sensitivity with subunit expression strengthens the hypothesis that the functional IHC cholinergic receptor is composed of both the alpha9 and alpha10 subunits and that the expression of the Acra10 gene is under the control of synaptic activity.