title: Plasma membrane mechanical stress activates TRPC5 channels.
abstract: Mechanical forces exerted on cells impose stress on the plasma membrane. Cells sense this stress and elicit a mechanoelectric transduction cascade that initiates compensatory mechanisms. Mechanosensitive ion channels in the plasma membrane are responsible for transducing the mechanical signals to electrical signals. However, the mechanisms underlying channel activation in response to mechanical stress remain incompletely understood. Transient Receptor Potential (TRP) channels serve essential functions in several sensory modalities. These channels can also participate in mechanotransduction by either being autonomously sensitive to mechanical perturbation or by coupling to other mechanosensory components of the cell. Here, we investigated the response of a TRP family member, TRPC5, to mechanical stress. Hypoosmolarity triggers Ca2+ influx and cationic conductance through TRPC5. Importantly, for the first time we were able to record the stretch-activated TRPC5 current at single-channel level. The activation threshold for TRPC5 was found to be 240 mOsm for hypoosmotic stress and between -20 and -40 mmHg for pressure applied to membrane patch. In addition, we found that disruption of actin filaments suppresses TRPC5 response to hypoosmotic stress and patch pipette pressure, but does not prevent the activation of TRPC5 by stretch-independent mechanisms, indicating that actin cytoskeleton is an essential transduction component that confers mechanosensitivity to TRPC5. In summary, our findings establish that TRPC5 can be activated at the single-channel level when mechanical stress on the cell reaches a certain threshold.
authors: School of Biomedical Sciences, Faculty of Medicine, the Chinese University of Hong Kong, Shatin, Hong Kong, China; Department of Physiology, Anhui Medical University, Hefei, China.
authors: Bing
authors: B
authors: Shen
authors: School of Biomedical Sciences, Faculty of Medicine, the Chinese University of Hong Kong, Shatin, Hong Kong, China.
authors: Ching-On
authors: CO
authors: Wong
authors: School of Biomedical Sciences, Faculty of Medicine, the Chinese University of Hong Kong, Shatin, Hong Kong, China.
authors: On-Chai
authors: OC
authors: Lau
authors: School of Biomedical Sciences, Faculty of Medicine, the Chinese University of Hong Kong, Shatin, Hong Kong, China.
authors: Theodosia
authors: T
authors: Woo
authors: Department of Physiology, Anhui Medical University, Hefei, China.
authors: Suwen
authors: S
authors: Bai
authors: School of Biomedical Sciences, Faculty of Medicine, the Chinese University of Hong Kong, Shatin, Hong Kong, China.
authors: Yu
authors: Y
authors: Huang
authors: School of Biomedical Sciences, Faculty of Medicine, the Chinese University of Hong Kong, Shatin, Hong Kong, China.
authors: Xiaoqiang
authors: X
authors: Yao
mesh_terms: D008841:Actin Cytoskeleton / Q000187:drug effects; D000818:Animals; D000906:Antibodies / Q000276:immunology; D016466:CHO Cells; D002118:Calcium / Q000378:metabolism; D002462:Cell Membrane / Q000378:metabolism*; D006224:Cricetinae; D003412:Cricetulus; D015638:Cytochalasin D / Q000494:pharmacology; D057809:HEK293 Cells; D006801:Humans; D040542:Mechanotransduction, Cellular / Q000502:physiology; D051379:Mice; D009997:Osmotic Pressure; D018408:Patch-Clamp Techniques; D013314:Stress, Mechanical; D050052:TRPC Cation Channels / Q000235:genetics / Q000276:immunology / Q000378:metabolism*
chemical_list: D000906:Antibodies; D050052:TRPC Cation Channels; C112021:Trpc5 protein, mouse; D015638:Cytochalasin D; D002118:Calcium