Philipp S, Hambrecht J, Braslavski L, Schroth G, Freichel M, Murakami M, Cavalié A, Flockerzi V
Institut für und Toxikologie der Universität des Saarlandes, Homburg/Saar, Germany.
EMBO J. 1998 Aug 3;17(15):4274-82. doi: 10.1093/emboj/17.15.4274.
In addition to voltage-gated calcium influx, capacitative calcium entry (CCE) represents a major pathway for calcium entry into the cell. Here we report the structure, expression and functional properties of a novel CCE channel, TRP5. This channel is a member of a new subfamily of mammalian homologues of the Drosophila transient receptor potential (TRP) protein, now comprising TRP5 (also CCE2) and the structurally related CCE1 (also TRP4). Like TRP4, TRP5 forms ion channels mainly permeable for Ca2+ which are not active under resting conditions but can be activated by manoeuvres known to deplete intracellular calcium stores. Accordingly, dialysis of TRP5-expressing cells with inositol-(1,4,5)-trisphosphate evokes inward rectifying currents which reversed polarity at potentials more positive than +30 mV. Ca2+ store depletion with thapsigargin induced TRP5-mediated calcium entry dependent on the concentration of extracellular calcium, as seen by dual wavelength fura-2 fluorescence ratio measurements. TRP5 transcripts are expressed almost exclusively in brain, where they are present in mitral cells of the olfactory bulb, in lateral cerebellar nuclei and, together with TRP4 transcripts, in CA1 pyramidal neurons of the hippocampus, indicating the presence of CCE channels in excitable cells and their participation in neuronal calcium homeostasis.
除了电压门控性钙内流外，钙池调控性钙内流（CCE）是钙进入细胞的主要途径。在此，我们报告一种新型CCE通道TRP5的结构、表达及功能特性。该通道是果蝇瞬时受体电位（TRP）蛋白的哺乳动物同源物新亚家族的成员，目前包括TRP5（也称为CCE2）和结构相关的CCE1（也称为TRP4）。与TRP4一样，TRP5形成主要对Ca2+通透的离子通道，在静息条件下不活跃，但可被已知能耗尽细胞内钙储存的操作激活。因此，用肌醇-（1,4,5）-三磷酸透析表达TRP5的细胞会诱发内向整流电流，该电流在电位高于+30 mV时极性反转。用毒胡萝卜素耗尽钙池可诱导TRP5介导的钙内流，这取决于细胞外钙的浓度，双波长fura-2荧光比率测量结果表明了这一点。TRP5转录本几乎只在脑中表达，存在于嗅球的二尖瓣细胞、外侧小脑核中，并且与TRP4转录本一起存在于海马体的CA1锥体神经元中，这表明可兴奋细胞中存在CCE通道，且它们参与神经元钙稳态。
