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The Journal of Neuroscience, February 14, 2007, 27(7):1566-1575; doi:10.1523/JNEUROSCI.4284-06.2007

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Cellular/Molecular
Effects of Body Temperature on Neural Activity in the Hippocampus: Regulation of Resting Membrane Potentials by Transient Receptor Potential Vanilloid 4

Koji Shibasaki,^1,2 Makoto Suzuki,³ Atsuko Mizuno,³ and Makoto Tominaga^1,2

¹Section of Cell Signaling, Okazaki Institute for Integrative Bioscience, National Institutes of Natural Sciences, Okazaki 444-8787, Japan, ²Department of Physiological Sciences, The Graduate University for Advanced Studies, Okazaki 444-8585, Japan, and ³Department of Pharmacology, Jichi Medical School, Minamikawachi, Tochigi 329-0498, Japan

Correspondence should be addressed to Makoto Tominaga, Section of Cell Signaling, Okazaki Institute for Integrative Bioscience, National Institutes of Natural Sciences, Okazaki, Aichi 444-8787, Japan. Email: tominaga{at}nips.ac.jp

Physiological body temperature is an important determinant for neural functions, and it is well established that changes in temperature have dynamic influences on hippocampal neural activities. However, the detailed molecular mechanisms have never been clarified. Here, we show that hippocampal neurons express functional transient receptor potential vanilloid 4 (TRPV4), one of the thermosensitive TRP (transient receptor potential) channels, and that TRPV4 is constitutively active at physiological temperature. Activation of TRPV4 at 37°C depolarized the resting membrane potential in hippocampal neurons by allowing cation influx, which was observed in wild-type (WT) neurons, but not in TRPV4-deficient (TRPV4KO) cells, although dendritic morphology, synaptic marker clustering, and synaptic currents were indistinguishable between the two genotypes. Furthermore, current injection studies revealed that TRPV4KO neurons required larger depolarization to evoke firing, equivalent to WT neurons, indicating that TRPV4 is a key regulator for hippocampal neural excitabilities. We conclude that TRPV4 is activated by physiological temperature in hippocampal neurons and thereby controls their excitability.

Key words: TRPV4; TRP channel; hippocampus; neural activity; synapse; body temperature

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Received June 11, 2006; revised Jan. 5, 2007; accepted Jan. 9, 2007.

Correspondence should be addressed to Makoto Tominaga, Section of Cell Signaling, Okazaki Institute for Integrative Bioscience, National Institutes of Natural Sciences, Okazaki, Aichi 444-8787, Japan. Email: tominaga{at}nips.ac.jp

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