Hypoosmotic- and pressure-induced membrane stretch activate TRPC5 channels
Hypoosmotic- and pressure-induced membrane stretch activate TRPC5 channels
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DOI：
10.1113/jphysiol.2008.161257
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发表时间：
2008-12-01
影响因子：
5.5
通讯作者：
Viana, Felix
中科院分区：
文献类型：
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作者：
Gomis, Ana;Soriano, Sergio;Viana, Felix
瞬时受体电位（TRP）通道介导了广泛的感觉功能。我们研究了TRPC 5的作用，TRPC 5是一种在中枢和外周神经系统中广泛表达的特征不明显的通道，作为一种潜在的神经感觉蛋白。在这里，我们表明，低渗刺激激活TRPC 5通道，导致大量的钙离子内流。对牵张诱导的膜牵张的反应被牵张激活离子通道的抑制剂GsMTx-4阻断。TRPC 5的直接低渗激活不依赖于磷脂酶C的功能。然而，在其中PIP 2水平通过脂质磷酸酶的受调节的过表达而降低的细胞系中，渗透反应被抑制。通过贴片移液管增加细胞内PIP 2水平恢复反应。在全细胞配置中，通过膜片移液管施加正压步骤来探测通道的机械敏感性。压力诱导的膜拉伸也激活TRPC 5通道，表明其作为一个换能器的机械刺激的作用。我们还证明了TRPC 5在感觉神经元中的表达，这与TRPC 5通道的机械特性一起表明其在机械感觉转导事件中的假定作用。
Transient receptor potential (TRP) channels mediate a wide array of sensory functions. We investigated the role of TRPC5, a poorly characterized channel widely expressed in the central and peripheral nervous system, as a potential osmosensory protein. Here we show that hypoosmotic stimulation activates TRPC5 channels resulting in a large calcium influx. The response to osmotically induced membrane stretch is blocked by GsMTx-4, an inhibitor of stretch activated ion channels. Direct hypoosmotic activation of TRPC5 is independent of phospholipase C function. However, the osmotic response is inhibited in a cell line in which PIP2 levels are reduced by regulated overexpression of a lipid phosphatase. The response was restored by increasing intracellular PIP2 levels through the patch pipette. The mechano-sensitivity of the channel was probed in the whole-cell configuration by application of steps of positive pressure through the patch pipette. Pressure-induced membrane stretch also activated TRPC5 channels, suggesting its role as a transducer of osmo-mechanical stimuli. We also demonstrated the expression of TRPC5 in sensory neurones which together with the osmo-mechanical characteristics of TRPC5 channels suggest its putative role in mechanosensory transduction events.