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The Journal of Neuroscience, February 2, 2005, 25(5):1304-1310; doi:10.1523/JNEUROSCI.4745.04.2005

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Behavioral/Systems/Cognitive
Altered Thermal Selection Behavior in Mice Lacking Transient Receptor Potential Vanilloid 4

Hyosang Lee,1 Tohko Iida,1 Atsuko Mizuno,2 Makoto Suzuki,2 and Michael J. Caterina1

1Departments of Biological Chemistry and Neuroscience, Johns Hopkins School of Medicine, Baltimore, Maryland 21205, and 2Department of Pharmacology, Jichi Medical School, Mimamikawachi, Tochigi 329-0498, Japan

Transient receptor potential vanilloid 4 (TRPV4), a cation channel responsive to hypotonicity, can also be activated by warm temperatures. Moreover, TRPV4-/- mice reportedly exhibit deficits in inflammation-induced thermal hyperalgesia. However, it is unknown whether TRPV4 or related transient receptor potential channels account for warmth perception under injury-free conditions. We therefore investigated the contribution of TRPV4 to thermosensation and thermoregulation in vivo. On a thermal gradient, TRPV4-/- mice selected warmer floor temperatures than wild-type littermates. In addition, whereas wild-type mice failed to discriminate between floor temperatures of 30 and 34°C, TRPV4-/- mice exhibited a strong preference for 34°C. TRPV4-/- mice also exhibited prolonged withdrawal latencies during acute tail heating. TRPV4-/- and wild-type mice exhibited similar changes in behavior on a thermal gradient after paw inflammation. Circadian body temperature fluctuations and thermoregulation in a warm environment were also indistinguishable between genotypes. These results demonstrate that TRPV4 is required for normal thermal responsiveness in vivo.

Key words: TRPV4; thermosensation; warm; heat; temperature; pain

Received Aug 19, 2004; revised December 23, 2004; accepted December 23, 2004.




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