Current Response in Ca _V 1.3^-/- Mouse Vestibular and Cochlear Hair Cells

Signal transmission by sensory auditory and vestibular hair cells relies upon Ca²⁺-dependent exocytosis of glutamate. The Ca²⁺ current in mammalian inner ear hair cells is predominantly carried through Ca _V 1.3 voltage-gated Ca²⁺ channels. Despite this, Ca _V 1.3 deficient mice (Ca _V 1.3^-/- ) are deaf but do not show any obvious vestibular phenotype. Here, we compared the Ca²⁺ current (I _Ca ) in auditory and vestibular hair cells from wild-type and Ca _V 1.3^-/- mice, to assess whether differences in the size of the residual I _Ca could explain, at least in part, the two phenotypes. Using 5 mM extracellular Ca²⁺ and near-body temperature conditions, we investigated the cochlear primary sensory receptors inner hair cells (IHCs) and both type I and type II hair cells of the semicircular canals. We found that the residual I _Ca in both auditory and vestibular hair cells from Ca _V 1.3^-/- mice was less than 20% (12-19%, depending on the hair cell type and age investigated) compared to controls, indicating a comparable expression of Ca _V 1.3 Ca²⁺ channels in both sensory organs. We also showed that, different from IHCs, type I and type II hair cells from Ca _V 1.3^-/- mice were able to acquire the adult-like K⁺ current profile in their basolateral membrane. Intercellular K⁺ accumulation was still present in Ca _V 1.3^-/- mice during I _K,L activation, suggesting that the K⁺-based, non-exocytotic, afferent transmission is still functional in these mice. This non-vesicular mechanism might contribute to the apparent normal vestibular functions in Ca _V 1.3^-/- mice.