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人胚肾293细胞中容积敏感阳离子通道TRP12(OTRPC4)的差异激活及容积调节性阴离子电流

Differential activation of the volume-sensitive cation channel TRP12 (OTRPC4) and volume-regulated anion currents in HEK-293 cells.

作者信息

Nilius B, Prenen J, Wissenbach U, Bödding M, Droogmans G

机构信息

Department of Physiology, Campus Gasthuisberg, KU Leuven, Herestraat 49, 3000 Leuven, Belgium.

出版信息

Pflugers Arch. 2001 Nov;443(2):227-33. doi: 10.1007/s004240100676.

DOI:10.1007/s004240100676
PMID:11713648
Abstract

The detection of changes in volume and osmolality is an essential function in vertebrate cells. A novel member of the transient receptor potential (trp) family of ion channels, which is sensitive to changes in cell volume, has been described recently. Heterologous expression of TRP12 in HEK cells resulted in the appearance of a swelling-activated cation current. The permeability sequence of this cation current for various monovalent cations, as determined from shifts in reversal potential upon extracellular cation substitution, was PK>PCs>PNa>PLi, corresponding to an Eisenman-IV sequence characteristic for a weak-field-strength site. Surprisingly, over-expression of this channel in HEK cells was accompanied by a dramatic down-regulation of the volume-regulated anion channel (VRAC), which is activated by cell swelling in non-transfected cells. In contrast to VRAC, TRP12 could not be activated at constant volume by a reduction of intracellular ionic strength or by intracellular perfusion with guanosine 5'-O-(3-thiotriphosphate (GTPgammaS). The kinetic and pharmacological profile of VRAC and TRP12 currents were also different.

摘要

检测体积和渗透压的变化是脊椎动物细胞的一项基本功能。最近描述了瞬时受体电位(trp)离子通道家族的一个新成员,它对细胞体积的变化敏感。TRP12在HEK细胞中的异源表达导致出现一种肿胀激活的阳离子电流。通过细胞外阳离子置换时反转电位的变化确定,这种阳离子电流对各种单价阳离子的通透性顺序为PK>PCs>PNa>PLi,这与弱场强位点的艾森曼-IV序列特征相对应。令人惊讶的是,该通道在HEK细胞中的过表达伴随着体积调节性阴离子通道(VRAC)的显著下调,VRAC在未转染细胞中由细胞肿胀激活。与VRAC不同,TRP12在恒定体积下不能通过降低细胞内离子强度或用鸟苷5'-O-(3-硫代三磷酸)(GTPγS)进行细胞内灌注来激活。VRAC和TRP12电流的动力学和药理学特征也不同。

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