L-type Ca channels play a crucial role for hearing. Deletion of the Ca_v1.3 Ca²⁺ channel has been shown to lead to deafness due to loss of Ca²⁺ -dependent transmitter release of inner hair cells (IHC). Surprisingly deafness in mutant mice is correlated with loss of outer (OHC) but not inner hair cells. This was unexpected as OHCs are primarily specializing in electromotility for sound amplification, so the existence of Ca²⁺ -activated exocytosis in OHCs was doubted since decades. In Ca _v1.3(-/-) mutant mice specifically OHCs in the low frequency regions exhibit sensitivity for lack of the Ca_v1.3 Ca²⁺ channel that resulted in degeneration around the onset of hearing (P12). In contrast, a normal phenotype and detectable distortion-product otoacoustic emissions (DPOAEs) indicated functional OHCs in the higher frequency range of the cochlea. Ca²⁺ currents of ~170 pA could be measured in neonatal Ca_v1.3 + /+ OHCs along the whole tonotopic axis. These currents declined in mature apical OHCs to ~50 pA at P12 and to 12 pA at P19. The more robust OHCs of the rat showed a similar developmental downregulation of the Ca²⁺ current amplitude that stabilized at ~60 pA. In particular in the low frequency regions of mature rat cochleae, Ca_v1.3 protein was visible in OHCs at places where afferent fibers make their contacts, in exact co-localization with the ribbon synapse protein CtBP2/RIBEYE. These findings strongly suggest a role of Ca_v1.3 channels for exocytosis in mature OHCs. Considering expected Ca²⁺ dependent processes in spiral ganglia neurons in addition to Ca_v1.3 other L-type Ca²⁺ channels may exist. As such Ca _v1.2 was detected in synaptic contacts of efferent fibres from the MOC (brainstem) as well as in spiral ganglia neurons.

Supported by DFG En-294/2-4.5; DFG Kni-316/3-1; 4-1, and Forschungs-schwerpunkt Baden-Wurttemberg