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The Journal of Neuroscience, August 1, 2002, 22(15):6408-6414
Heat-Evoked Activation of the Ion Channel, TRPV4
Ali Deniz
Güler1,
Hyosang
Lee1,
Tohko
Iida2,
Isao
Shimizu1, 3,
Makoto
Tominaga2, and
Michael
Caterina1
1 Departments of Biological Chemistry and Neuroscience,
Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, 2 Department of Physiology, Mie University School of
Medicine, Tsu/Mie 514-8507, Japan, and 3 Dainippon
Pharmaceutical Company, Limited, Suita/Osaka 564-0053, Japan
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.
Key words:
TRPV4; OTRPC4; VR-OAC; VRL-2; TRP12; heat; ion channel; thermotransduction; osmolarity; hypothalamus
Copyright © 2002 Society for Neuroscience 0270-6474/02/22156408-07$05.00/0
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