Effects of body temperature on neural activity in the hippocampus: Regulation of resting membrane potentials by transient receptor potential vanilloid 4
Effects of body temperature on neural activity in the hippocampus: Regulation of resting membrane potentials by transient receptor potential vanilloid 4
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DOI：
10.1523/jneurosci.4284-06.2007
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发表时间：
2007-02-14
影响因子：
5.3
通讯作者：
Tominaga, Makoto
中科院分区：
文献类型：
--
作者：
Shibasaki, Koji;Suzuki, Makoto;Tominaga, Makoto
生理体温是神经功能的重要决定因素，并且众所周知，温度的变化对海马神经活动具有动态影响。然而，详细的分子机制尚未阐明。在这里，我们证明海马神经元表达功能性瞬时受体电位香草酸 4 (TRPV4)，这是热敏 TRP（瞬时受体电位）通道之一，并且 TRPV4 在生理温度下具有持续活性。 TRPV4在37℃下激活，通过允许阳离子流入，使海马神经元的静息膜电位去极化，这在野生型（WT）神经元中观察到，但在TRPV4缺陷（TRPV4KO）细胞中没有观察到，尽管两种基因型之间的树突形态、突触标记聚类和突触电流无法区分。此外，目前的注射研究表明，TRPV4KO 神经元需要更大的去极化才能引起放电，与 WT 神经元相当，表明 TRPV4 是海马神经兴奋性的关键调节因子。我们得出结论，TRPV4 被海马神经元的生理温度激活，从而控制其兴奋性。
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.