Functional properties and ion channels mediating acetylcholine release at the mouse medial olivocochlear-outer hair cell synapse at the onset of hearing

PAUL FUCHS; LUCAS VATTINO; ELEONORA KATZ; ANA BELÉN ELGOYHEN

CABA

Congreso; FALAN Congress 2016; 2016

Federation of Latin American and Caribbean Neuroscience Societies

The mammalian auditory epithelium contains two types of mechanosensory cells, inner (IHC) and outer (OHC) hair cells. IHC convey acoustic stimuli to the central nervous system while OHCs are implicated in sound amplification. Medial olivocochlear (MOC) efferent fibers start to innervate the OHCs at postnatal day (P)6. Since birth to hearing onset MOC fibers also innervate the IHCs. At P9-11, ACh release at the MOC-IHC synapse is supported by P/Q- and N-type voltage-gated Ca2+ channels (VGCC) and negatively regulated by L-type VGCC coupled to BK channels. However, at earlier stages (P5), N-type VGCC are not involved and release is mediated by P/Q- and R-type VGCCs. At this stage, L-type VGCCs have a dual role: they activate BK channels and support release. Using isolated cochleas at P11-13 we show by whole-cell voltage-clamp recordings in OHCs while stimulating the efferent axons, that P/Q- and R-type VGCC support release at MOC-OHC synapses (200 nM o-AgaVIA and 500 nM SNX482 blocked responses by 74% and 60%, respectively) whereas N-type VGCC are not involved (500 nM o-conotoxinIVA had no effect). Moreover, experiments with iberiotoxin (BK channel antagonist), BayK and nifedipine (L-type VGCC agonist and antagonist, respectively) showed that L-type VGCC both support release and activate BK channels, indicating less compartmentalization of presynaptic release components. This is identical to the MOC-IHC synapse at early immature stages.Support:UBA&ANPCyT:EK,ABE; NIH: PAF,ABE.