Differential activation of the volume-sensitive cation channel TRP12 (OTRPC4) and volume-regulated anion currents in HEK-293 cells
Differential activation of the volume-sensitive cation channel TRP12 (OTRPC4) and volume-regulated anion currents in HEK-293 cells
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DOI：
10.1007/s004240100676
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发表时间：
2001-11-01
影响因子：
4.5
通讯作者：
Droogmans, G
中科院分区：
文献类型：
--
作者：
Nilius, B;Prenen, J;Droogmans, G
检测体积和渗透压的变化是脊椎动物细胞的基本功能。瞬时受体电位（trp）离子通道家族的一个新成员，对细胞体积的变化敏感，最近被描述。TRP 12在HEK细胞中的异源表达导致了肿胀激活的阳离子电流的出现。从细胞外阳离子取代后的反转电位的变化确定的这种阳离子电流对各种单价阳离子的渗透性顺序为P-K>P-Cs>P-Na>P-Li，对应于弱场强位点的Eisenman-IV序列特征。令人惊讶的是，HEK细胞中该通道的过表达伴随着体积调节阴离子通道（VRAC）的显著下调，该通道在未转染细胞中被细胞肿胀激活。与VRAC相比。TRP 12不能通过降低细胞内离子强度或通过用鸟苷5 ′-O-（3 -硫代三磷酸）（GTP γ S）进行细胞内灌注而在恒定体积下被激活。VRAC和TRP 12电流的动力学和药理学特征也不同。
The detection of changes in volume and osmolatity 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 P-K>P-Cs>P-Na>P-Li, 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 (GTP gammaS). The kinetic and pharmacological profile of VRAC and TRP12 currents were also different.