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

1 Center for Neuroscience and 2 Program in Communication Science, University of California Davis, Davis, California; 3 Department of Nephrology, Xijing Hospital, The Fourth Military Medical University, Xi'an, China; 4 Department of Otorhinolaryngology, University of Pennsylvania, Philadelphia, Pennsylvania; 5 Department of Physiology and Biophysics, University of Miami School of Medicine, Miami, Florida; and 6 School of Biological Sciences, University of Sussex, Brighton, United Kingdom Submitted 26 June 2008; accepted in final form 12 August 2008 The molecular identity of non-Ca v 1.3 channels in auditory and vestibular hair cells has remained obscure, yet the evidence in support of their roles to promote diverse Ca 2+ -dependent functions is indisputable. Recently, a transient Ca v 3.1 current that serves as a functional signature for the development and regeneration of hair cells has been identified in the chicken basilar papilla. The Ca v 3.1 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 Ca v 3.1 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 Ca 2+ 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 Ca v 3.1 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 Ca v 3.1 channel may have contributed to the difficulties associated with identification of the non-Ca v 1.3 currents. Address for reprint requests and other correspondence: E. N. Yamoah, Center for Neuroscience, Program in Communication Science, University of California, Davis, 1544 Newton Ct., Davis, CA 95618 (E-mail: enyamoah{at}ucdavis.edu )