title: Redox-sensitive transient receptor potential channels in oxygen sensing and adaptation.
abstract: Regulation of ion channels is central to the mechanisms that underlie immediate acute physiological responses to changes in the availability of molecular oxygen (O2). A group of cation-permeable channels that are formed by transient receptor potential (TRP) proteins have been characterized as exquisite sensors of redox reactive species and as efficient actuators of electric/ionic signals in vivo. In this review, we first discuss how redox-sensitive TRP channels such as TRPA1 have recently emerged as sensors of the relatively inert oxidant O2. With regard to the physiological significance of O2 sensor TRP channels, vagal TRPA1 channels are mainly discussed with respect to their role in respiratory regulation in comparison with canonical pathways in glomus cells of the carotid body, which is a well-established O2-sensing organ. TRPM7 channels are discussed regarding hypoxia-sensing function in ischemic cell death. Also, ubiquitous expression of TRPA1 and TRPM7 together with their physiological relevance in the body is examined. Finally, based upon these studies on TRP channels, we propose a hypothesis of "O2 remodeling." The hypothesis is that cells detect deviation of O2 availability from appropriate levels via sensors and adjust local O2 environments in vivo by controlling supply and consumption of O2 via pathways comprising cellular signals and transcription factors downstream of sensors, which consequently optimize physiological functions. This new insight into O2 adaptation through ion channels, particularly TRPs, may foster a paradigm shift in our understanding in the biological significance of O2.
authors.affiliation: Laboratory of Molecular Biology, Department of Synthetic Chemistry and Biological Chemistry, Graduate School of Engineering, Kyoto University, Nishikyo-ku, Kyoto, 615-8510, Japan. mori@sbchem.kyoto-u.ac.jp.|Laboratory of Environmental Systems Biology, Department of Technology and Ecology, Hall of Global Environmental Studies, Kyoto University, Nishikyo-ku, Kyoto, 615-8510, Japan. mori@sbchem.kyoto-u.ac.jp.
authors.forename: Yasuo
authors.initials: Y
authors.lastname: Mori
authors.affiliation: Laboratory of Molecular Biology, Department of Synthetic Chemistry and Biological Chemistry, Graduate School of Engineering, Kyoto University, Nishikyo-ku, Kyoto, 615-8510, Japan.|Department of Cell Biology, Harvard Medical School, Boston, MA, 02115, USA.
authors.forename: Nobuaki
authors.initials: N
authors.lastname: Takahashi
authors.affiliation: Laboratory of Molecular Biology, Department of Synthetic Chemistry and Biological Chemistry, Graduate School of Engineering, Kyoto University, Nishikyo-ku, Kyoto, 615-8510, Japan.
authors.forename: Onur Kerem
authors.initials: OK
authors.lastname: Polat
authors.affiliation: Laboratory of Molecular Biology, Department of Synthetic Chemistry and Biological Chemistry, Graduate School of Engineering, Kyoto University, Nishikyo-ku, Kyoto, 615-8510, Japan.
authors.forename: Tatsuki
authors.initials: T
authors.lastname: Kurokawa
authors.affiliation: Department of Cardiovascular Medicine, Graduate School of Medicine, The University of Tokyo, Bunkyo-ku, Tokyo, 113-8655, Japan.
authors.forename: Norihiko
authors.initials: N
authors.lastname: Takeda
authors.affiliation: Department of Biochemistry, Osaka Medical Center for Cancer and Cardiovascular Diseases, Higashinari-ku, Osaka, 537-8511, Japan.
authors.forename: Masahiro
authors.initials: M
authors.lastname: Inoue
mesh_terms: D000222:Adaptation, Physiological; D000818:Animals; D002344:Carotid Body / Q000378:metabolism*; D006801:Humans; D010084:Oxidation-Reduction; D010100:Oxygen / Q000378:metabolism*; D050052:TRPC Cation Channels / Q000235:genetics / Q000378:metabolism*
chemical_list: D050052:TRPC Cation Channels; D010100:Oxygen
keywords: Carotid body; Hypoxia; Oxygen; TRP channels; Vagus