Molecular identity and functional properties of a novel T-type Ca2+ channel cloned from the sensory epithelia of the mouse inner ear
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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DOI：
10.1152/jn.90707.2008
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发表时间：
2008-10-01
影响因子：
2.5
通讯作者：
Yamoah, Ebenezer N.
中科院分区：
文献类型：
--
作者：
Nie, Liping;Zhu, Jun;Yamoah, Ebenezer N.
听觉和前庭毛细胞中非钙(V)1.3通道的分子特性尚不清楚，但支持其促进多种钙依赖功能的证据是毋庸置疑的。最近，在鸡的基底乳头中发现了一种瞬时Ca(V)3.1电流，它是毛细胞发育和再生的功能标志。钙(V)3.1电流促进发育中的毛细胞的自发活动，这可能是突触形成所必需的。在这里，我们已经分离并测序了小鼠内耳中一种不同的Ca(V)3.1亚型的全长互补DNA。该通道来自外显子14、外显子25A、外显子34和外显子35的选择性剪接。该通道在非洲爪哇卵母细胞中的功能表达产生了钙电流，其通透表型与T型通道一致。然而，与大多数多离子通道不同的是，T型通道不表现出异常的摩尔分数效应，可能反映了类似的二价阳离子的渗透特性。Ca(V)3.1通道表达于内耳的感觉和无感觉上皮细胞。此外，在发育过程中，表达水平也发生了深刻的变化。该通道在发育过程中的差异表达和内耳Ca(V)3.1通道的药理学可能是导致识别非Ca(V)1.3电流的困难的原因之一。
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 Ca2+ -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 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 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.