Current Response in CaV1.3–/– Mouse Vestibular and Cochlear Hair Cells
Marco Manca, Piece Yen, Paolo Spaiardi, Giancarlo Russo, Roberta Giunta, Stuart L. Johnson, Walter Marcotti, Sergio Masetto
Abstract
Signal transmission by sensory auditory and vestibular hair cells relies upon Ca 2+ -dependent exocytosis of glutamate. The Ca 2+ current in mammalian inner ear hair cells is predominantly carried through Ca V 1.3 voltage-gated Ca 2+ 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 Ca 2+ 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 Ca 2+ 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 Ca 2+ 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.