Molecular Identity and Functional Properties of a Novel T-Type Ca2+ Channel Cloned From the Sensory Epithelia of the Mouse Inner Ear

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Abstract
The molecular identity of non-Cav1.3 channels in auditory and vestibular hair cells has remained obscure, yet the evidence in support of their roles to promote diverse Ca2+-dependent functions is indisputable. Recently, a transient Cav3.1 current that serves as a functional signature for the development and regeneration of hair cells has been identified in the chicken basilar papilla. The Cav3.1 current promotes spontaneous activity of the developing hair cell, which may be essential for synapse formation. Here, we have isolated and sequenced the full-length complementary DNA of a distinct isoform of Cav3.1 in the mouse inner ear. The channel is derived from alternative splicing of exon14, exon25A, exon34, and exon35. Functional expression of the channel in Xenopus oocytes yielded Ca2+ currents, which have a permeation phenotype consistent with T-type channels. However, unlike most multiion channels, the T-type channel does not exhibit the anomalous mole fraction effect, possibly reflecting comparable permeation properties of divalent cations. The Cav3.1 channel was expressed in sensory and nonsensory epithelia of the inner ear. Moreover, there are profound changes in the expression levels during development. The differential expression of the channel during development and the pharmacology of the inner ear Cav3.1 channel may have contributed to the difficulties associated with identification of the non-Cav1.3 currents.

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