title: Heat-evoked activation of the ion channel, TRPV4.
abstract: The mammalian nervous system constantly evaluates internal and environmental temperatures to maintain homeostasis and to avoid thermal extremes. Several members of the transient receptor potential (TRP) family of ion channels have been implicated as transducers of thermal stimuli, including TRPV1 and TRPV2, which are activated by heat, and TRPM8, which is activated by cold. Here we demonstrate that another member of the TRP family, TRPV4, previously described as a hypo-osmolarity-activated ion channel, also can be activated by heat. In response to warm temperatures, TRPV4 mediates large inward currents in Xenopus oocytes and both inward currents and calcium influx into human embryonic kidney 293 cells. In both cases these responses are observed at temperatures lower than those required to activate TRPV1 and can be inhibited reversibly by ruthenium red. Heat-evoked TRPV4-mediated responses are greater in hypo-osmotic solutions and reduced in hyperosmotic solutions. Consistent with these functional properties, we observed TRPV4 immunoreactivity in anterior hypothalamic structures involved in temperature sensation and the integration of thermal and osmotic information. Together, these data implicate TRPV4 as a possible transducer of warm stimuli within the hypothalamus.
authors.affiliation: Department of Biological Chemistry, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA.
authors.forename: Ali Deniz
authors.initials: AD
authors.lastname: Güler
authors.forename: Hyosang
authors.initials: H
authors.lastname: Lee
authors.forename: Tohko
authors.initials: T
authors.lastname: Iida
authors.forename: Isao
authors.initials: I
authors.lastname: Shimizu
authors.forename: Makoto
authors.initials: M
authors.lastname: Tominaga
authors.forename: Michael
authors.initials: M
authors.lastname: Caterina
mesh_terms: D000818:Animals; D001833:Body Temperature Regulation / Q000502:physiology; D002118:Calcium / Q000378:metabolism; D027682:Cation Transport Proteins; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005456:Fluorescent Dyes; D006358:Hot Temperature; D006801:Humans; D007032:Hypothalamus, Anterior / Q000166:cytology / Q000378:metabolism*; D007150:Immunohistochemistry; D007473:Ion Channels / Q000235:genetics / Q000378:metabolism*; D007668:Kidney / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D009865:Oocytes / Q000166:cytology / Q000378:metabolism; D009994:Osmolar Concentration; D018408:Patch-Clamp Techniques; D011301:Preoptic Area / Q000166:cytology / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D050916:TRPV Cation Channels; D013696:Temperature; D014162:Transfection; D014982:Xenopus laevis
chemical_list: D027682:Cation Transport Proteins; D004791:Enzyme Inhibitors; D005456:Fluorescent Dyes; D007473:Ion Channels; D012333:RNA, Messenger; D050916:TRPV Cation Channels; C416986:TRPV4 protein, human; C486577:Trpv4 protein, rat; D002118:Calcium