Current Response in Ca V 1.3-/- Mouse Vestibular and Cochlear Hair Cells.

Marco Manca,Sergio Masetto,Walter Marcotti,Roberta Giunta,Paolo Spaiardi,Piece Yen,Stuart L Johnson,Giancarlo Russo

doi:10.3389/fnins.2021.749483

Marco Manca, Sergio Masetto + Show 6 more

Open Access

https://doi.org/10.3389/fnins.2021.749483

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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.

Highlights

The inner ear houses the auditory and the balance organs
Progressive intercellular K+ accumulation during depolarization is responsible for the “apparent” inactivation of the outward current, which is due to the progressive decrease of the driving force for K+ to exit the hair cells (e.g., Spaiardi et al, 2017)
We investigated whether the normal developmental acquisition of the maturelike K+ current in the crista hair cells was dependent on the presence of CaV 1.3 Ca2+ channels, as previous demonstrated for the inner hair cells (IHCs) (Brandt et al, 2003; Jeng et al, 2020a)

Summary

INTRODUCTION

The inner ear houses the auditory and the balance organs. In mammals, the primary sensory cells are the inner hair cells (IHCs) of the cochlea, and the type I and type II hair cells of the vestibular system. Acoustic stimuli or head movements cause change in the hair cell membrane potential, which modulates Ca2+ inflow and related neurotransmitter (glutamate) exocytosis (Bonsacquet et al, 2006; Dulon et al, 2009; Songer and Eatock, 2013; Sadeghi et al, 2014; Vincent et al, 2014; Kirk et al, 2017) Both auditory and vestibular hair cells express voltage-gated L-type Ca2+ channels containing the pore-forming CaV 1.3 subunit (previously known as α1D), which are characterized by a negative voltage of activation (about −60 mV) and negligible voltage-dependent. Since IK,L and intercellular K+ accumulation in the synaptic cleft of type I hair cells were normal in CaV 1.3−/− mice, non-quantal signal transmission might contribute to the vestibular functioning of CaV 1.3−/− mice

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RESULTS

DISCUSSION