Presynaptic voltage-gated Ca2+ channels differentially contribute to transmitter release at the mouse medial olivocochlear-outer hair cell synapse at two postnatal stages.

VATTINO L; ELGOYHEN AB; KATZ E

Congreso; 2018 Meedwindetr Meeting ARO; 2018

In mammals, outer hair cells (OHCs) of the organ of Corti undergo voltage-dependent changes in length and stiffness, a process known as electromotility. This amplifies movement of the basilar membrane, increasing the gain and tuning of acoustic inputs. 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 inner hair cells (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, ion channels coupled to this process at the MOC-OHC synapse are unknown. , By using whole-cell voltage-clamp recordings in OHCs while electrically stimulating the efferent axons in acutely isolated mouse cochleas we show 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