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 CaV1.3 voltage-gated Ca2+ channels. Despite this, CaV1.3 deficient mice (CaV1.3−/−) are deaf but do not show any obvious vestibular phenotype. Here, we compared the Ca2+ current (ICa) in auditory and vestibular hair cells from wild-type and CaV1.3−/− mice, to assess whether differences in the size of the residual ICa 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 ICa in both auditory and vestibular hair cells from CaV1.3−/− mice was less than 20% (12–19%, depending on the hair cell type and age investigated) compared to controls, indicating a comparable expression of CaV1.3 Ca2+ channels in both sensory organs. We also showed that, different from IHCs, type I and type II hair cells from CaV1.3−/− mice were able to acquire the adult-like K+ current profile in their basolateral membrane. Intercellular K+ accumulation was still present in CaV1.3−/− mice during IK,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 CaV1.3−/− mice.

Current Response in CaV1.3–/– Mouse Vestibular and Cochlear Hair Cells

Manca, Marco;Spaiardi, Paolo;Russo, Giancarlo;Giunta, Roberta;Masetto, Sergio
2021

Abstract

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 CaV1.3 voltage-gated Ca2+ channels. Despite this, CaV1.3 deficient mice (CaV1.3−/−) are deaf but do not show any obvious vestibular phenotype. Here, we compared the Ca2+ current (ICa) in auditory and vestibular hair cells from wild-type and CaV1.3−/− mice, to assess whether differences in the size of the residual ICa 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 ICa in both auditory and vestibular hair cells from CaV1.3−/− mice was less than 20% (12–19%, depending on the hair cell type and age investigated) compared to controls, indicating a comparable expression of CaV1.3 Ca2+ channels in both sensory organs. We also showed that, different from IHCs, type I and type II hair cells from CaV1.3−/− mice were able to acquire the adult-like K+ current profile in their basolateral membrane. Intercellular K+ accumulation was still present in CaV1.3−/− mice during IK,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 CaV1.3−/− mice.
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/11571/1445914
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