Effects of body temperature on neural activity in the hippocampus: regulation of resting membrane potentials by transient receptor potential vanilloid 4.
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 degrees 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.
Shibasaki
Koji
K
Section of Cell Signaling, Okazaki Institute for Integrative Bioscience, National Institutes of Natural Sciences, Okazaki 444-8787, Japan.
Suzuki
Makoto
M
Mizuno
Atsuko
A
Tominaga
Makoto
M
D000818:Animals; D000831:Animals, Newborn; D001253:Astrocytes; D001831:Body Temperature; D002118:Calcium / Q000378:metabolism; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology; D015870:Gene Expression / Q000502:physiology; D049452:Green Fluorescent Proteins / Q000378:metabolism; D006624:Hippocampus / Q000166:cytology*; D006801:Humans; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D008564:Membrane Potentials / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009419:Nerve Tissue Proteins / Q000378:metabolism; D009474:Neurons / Q000145:classification / Q000187:drug effects / Q000502:physiology* / Q000528:radiation effects; D018408:Patch-Clamp Techniques / Q000379:methods; D010703:Phorbol Esters / Q000494:pharmacology; D012333:RNA, Messenger / Q000096:biosynthesis; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D050916:TRPV Cation Channels / Q000172:deficiency / Q000502:physiology*
D018690:Excitatory Amino Acid Agonists; D009419:Nerve Tissue Proteins; D010703:Phorbol Esters; D012333:RNA, Messenger; D050916:TRPV Cation Channels; C486576:Trpv4 protein, mouse; D049452:Green Fluorescent Proteins; C008876:phorbol-12,13-didecanoate; D002118:Calcium