Differential contribution of presynaptic calcium channels to synaptic transmission at the mouse medial olivocochlear-outer hair cell synapse at two developmental stages

LUCAS VATTINO; ANA BELÉN ELGOYHEN; ELEONORA KATZ

Washington

Congreso; Society For Neuroscience Meeting; 2017

Society For Neuroscience Org.

The mammalian auditory epithelium contains two types of mechanosensory cells, inner and outer hair cells (IHCs and OHCs, respectively). IHCs transduce sound stimuli into electrical signals that travel to the central nervous system while the OHCs, by virtue of their electromotile properties, are mainly involved in sound amplification. OHC electromotility is regulated by descending medial olivocochlear (MOC) fibers. The MOC-OHC synapse is cholinergic and inhibitory and is mediated by the α9α10 cholinergic nicotinic receptor coupled to the activation of Ca2+-activated K+ channels that hyperpolarize the OHCs. During development, before reaching the OHCs, MOC fibers transiently innervate the IHCs (from birth to hearing onset, postnatal day (P)12 in mice). The ion channels coupled to transmitter release at the MOC-IHC synapse have been previously described (Zorrilla de San Martin et al., 2010), however, nothing is known about the ion channels coupled to this process at the MOC-OHC synapse. Using acutely isolated mouse cochleas we show, by whole-cell voltage-clamp recordings in OHCs while electrically stimulating the efferent axons, that ACh release is mediated by both P/Q and R-type voltage-gated Ca2+ channels (VGCC) at P11-13 and by P/Q- and N-type VGCCs at P20-22. In addition, we show that at P11-13, large conductance Ca2+-activated K+ channels (BK) are functionally expressed at the MOC-OHC synapse as block by iberiotoxin (200 nM) significantly increases release (control 0.16±0.02; Ibtx 0.30±0.05, n=7; p