Ion channels and synaptic transmission at the mouse medial olivocochlear-outer hair cell synapse around the onset of hearing

ELEONORA KATZ; LUCAS G. VATTINO; A. BELÉN ELGOYHEN

Buenos Aires

Congreso; Fronteras en Biociencias 2; 2016

Instituto de Investigación en Biomedicina de Buenos Aires, CONICET-Instituto Partner de la Sociedad Max Planck

The organ of Corti, the mammalian auditory epithelium contains two types of mechanosensory cells, inner (IHC) and outer (OHC) hair cells. IHCs convey acoustic stimuli to the central nervous system while OHCs are implicated in sound amplification and in the fine tuning of the basilar membrane. Medial olivocochlear (MOC) fibers begin to innervate outer hair cells (OHCs), the final targets of this efferent system, at postnatal day (P) 6. From birth to hearing onset (around P12 in rodents) MOC fibers transiently innervate inner hair cells (IHCs). At P9-11, acetylcholine (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 large conductance Ca2+- and voltage-activated potassium (BK) channels. However, at earlier stages (P5), N-type VGCC are not functionally expressed at the MOC synaptic terminals and ACh release is mediated by P/Q- and R-type VGCCs. At this stage, Ca2+ flowing in through L-type VGCCs plays a dual role: it both activates BK channels and supports ACh release. In the present work, 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 ω-AgaVIA and 500 nM SNX482 blocked responses by 74% and 60%, respectively) whereas N-type VGCC are not implicated (500 nM ω-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, suggesting less compartmentalization of presynaptic molecules involved in transmitter release. This resembles the MOC-IHC synapse at early immature stages (P5) and suggests that the MOC-OHCs synapse is functionally immature at the onset of hearing.Support:UBA&ANPCyT:EK,ABE; NIH:ABE, PAF.