RT Journal Article SR Electronic T1 Heat-Evoked Activation of the Ion Channel, TRPV4 JF The Journal of Neuroscience JO J. Neurosci. FD Society for Neuroscience SP 6408 OP 6414 DO 10.1523/JNEUROSCI.22-15-06408.2002 VO 22 IS 15 A1 Güler, Ali Deniz A1 Lee, Hyosang A1 Iida, Tohko A1 Shimizu, Isao A1 Tominaga, Makoto A1 Caterina, Michael YR 2002 UL http://www.jneurosci.org/content/22/15/6408.abstract AB 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.