Plant Tim D
Pharmakologisches Institut, BPC-Marburg, FB-Medizin, Philipps-Universität Marburg, Karl-von-Frisch-Straße 1, 35032, Marburg, Germany,
Handb Exp Pharmacol. 2014;223:743-66. doi: 10.1007/978-3-319-05161-1_2.
Mechanosensitive channels allow cells to respond to changes in membrane stretch that occur due to external stimuli like pressure or flow or that occur because of osmotically induced cell swelling or shrinkage. Ion fluxes through the channels change the membrane potential and ion concentrations and link the stretch to cellular signalling. Changes in cellular activity evoked by mechanical stimuli can be used to elicit local tissue responses or can be transmitted further to generate more widespread responses. Channels can respond directly to membrane stress, can be conferred mechanosensitive by interaction with structural proteins, or can be activated by mechanosensitive signalling pathways. Because mechanosensitive channels are often nonselective cation channels, and invertebrate TRP isoforms are involved in mechanosensation, many of the mammalian TRP isoforms have been investigated with regard to their mechanosensitivity. There is evidence that members of the TRPC, TRPV, TRPM, TRPA and TRPP subfamilies could be in some way mechanosensitive, and each of the activation mechanisms described above is used by a TRP channel. TRP channels may be involved in mechanosensitive processes ranging from flow and pressure sensing in the vasculature and other organs to mechanosensation in sensory neurones and sensory organs. There is also evidence for a role of mechano- or osmosensitive TRP isoforms in osmosensing and the regulation of cell volume. Often, a number of different TRP isoforms have been implicated in a single type of mechanosensitive response. In many cases, the involvement of the isoforms needs to be confirmed, and their exact role in the signalling process determined.
机械敏感通道使细胞能够对因外部刺激(如压力或流体流动)或渗透诱导的细胞肿胀或收缩而发生的膜拉伸变化做出反应。通过这些通道的离子通量会改变膜电位和离子浓度,并将拉伸与细胞信号传导联系起来。机械刺激引起的细胞活动变化可用于引发局部组织反应,或进一步传递以产生更广泛的反应。通道可以直接对膜应力做出反应,可以通过与结构蛋白相互作用而具有机械敏感性,或者可以由机械敏感信号通路激活。由于机械敏感通道通常是非选择性阳离子通道,并且无脊椎动物的瞬时受体电位(TRP)亚型参与机械感觉,因此许多哺乳动物的TRP亚型已就其机械敏感性进行了研究。有证据表明,TRPC、TRPV、TRPM、TRPA和TRPP亚家族的成员可能在某种程度上具有机械敏感性,并且上述每种激活机制都被一种TRP通道所采用。TRP通道可能参与从血管系统和其他器官中的流体流动和压力感知到感觉神经元和感觉器官中的机械感觉等机械敏感过程。也有证据表明机械或渗透压敏感的TRP亚型在渗透压感知和细胞体积调节中起作用。通常,多种不同的TRP亚型与单一类型的机械敏感反应有关。在许多情况下,这些亚型的参与需要得到证实,并且它们在信号传导过程中的确切作用需要确定。