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The study of physiological role of the splice variants of T-type calcium channel that present in human myometrial smooth muscle.

研究人类子宫肌层平滑肌中 T 型钙通道剪接变体的生理作用。

基本信息

批准号：
17591767
负责人：
INOUE Yoshihito
金额：
$ 1.82万
依托单位：
Fukuoka University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2005
资助国家：
日本
起止时间：
2005 至 2007
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-17591767/
关键词：
human myometrial smooth muscle voltage clamp T-type calcium channel splice variant cDNA Xenopus oocyte

项目摘要

Electrophysiological characteristics were compared among four cloned human α1H isoforms transcripted by alternative splicings of exons 25B and 26 [ΔA25B/+26 (native form; α1H-a), Δ25B/Δ26 (α1H-b), +25B/Δ26, and +25B/+26] in the intracellular loop between domains III and IV (III-IV linker) of a human T-type calcium channel (Cav3.2). The native isoform Δ25B/+26 predominated in ovary and non-pregnant uterus, while isoform Δ25B/Δ26 (α1H-b) predominated in pregnant uterus and testis. Expressions of the newly identified +25B/Δ26 and +25B/+26 isoforms were greater in the uterus at gestation than in the nonpregnant uterus. When expressed in Xenopus laevis oocytes, all isoforms produced transient inward currents with low voltage-dependent activation and inactivation characterized in typical T-type Ca^<2+> currents. Each isoform possessing exon 25B (+25B/Δ26 or +25B/+26) showed current activation and inactivation at a more negative membrane potential than the respective isoform (Δ25B/Δ26 or Δ25B/+26) lacking it. Moreover, the current activation and inactivation rates were faster for the two isoforms possessing exon 25B than for the respective isoforms lacking it. By itself, exon 26 seemed not to affect any electrophysiological characteristics. Increasing the net positive charge (relative to the native form), as occurred in isoforms Δ25B/Δ26, +25B/Δ26, and +25B1+26, caused recovery from short-term inactivation to become faster. On the other hand, only Δ25B/Δ26 isoforms existed in non-pregnant myometrium with the similar electrical properties to that in pregnant myometrium. Onr results show that molecular structure variations within the III-IV linker influence the voltage-dependence and kinetics of both activation and inactivation. Although the role of T-type Ca^<2+> channels in uterine tissue remains unknown, changes in the uterine expression of these α1H isoforms may influence physiological functions during pregnancy.

比较了4种克隆的人α1H亚型的电生理特性，这些亚型是通过人T型钙通道（Cav3.2）结构域III和IV之间的胞内环（III-IV接头）中外显子25 B和26的交替剪接[Δ A25 B/+26（天然形式; α1H-a）、Δ 25 B/Δ 26（α1H-b）、+25 B/Δ26和+25 B/+26]转录的。天然亚型Δ 25 B/+26在卵巢和非妊娠子宫中占优势，而亚型Δ 25 B/Δ26（α1H-b）在妊娠子宫和睾丸中占优势。新鉴定的+25 B/Δ26和+25 B/+26亚型在妊娠子宫中的表达高于非妊娠子宫。当在非洲爪蟾卵母细胞中表达时，所有亚型均产生瞬时内向电流，其特征为典型的T型Ca^2+电流，具有低电压依赖性激活和失活。每个亚型具有外显子25 B（+25 B/Δ26或+25 B/+26）在比相应亚型更负的膜电位下显示电流激活和失活此外，具有外显子25 B的两种同种型的电流激活和失活速率比缺乏外显子25 B的相应同种型快。外显子26似乎不影响任何电生理特征。增加净正电荷（相对于天然形式），如亚型Δ 25 B/Δ26、+25 B/Δ26和+25 B1 +26中所发生的那样，导致从短期失活中恢复得更快。另一方面，在非妊娠子宫肌层中仅存在Δ 25 B/Δ26亚型，其电特性与妊娠子宫肌层相似。Onr结果表明，III-IV接头内的分子结构变化影响激活和失活的电压依赖性和动力学。虽然T型Ca^<2+>通道在子宫组织中的作用尚不清楚，但这些α 1 H亚型在子宫中表达的变化可能会影响妊娠期间的生理功能。