Molecular Transient Receptor Potential Vanilloid 1 Is Required for Intrinsic Osmoreception in Organum Vasculosum Lamina Terminalis Neurons and for Normal Thirst Responses to Systemic Hyperosmolality
Molecular Transient Receptor Potential Vanilloid 1 Is Required for Intrinsic Osmoreception in Organum Vasculosum Lamina Terminalis Neurons and for Normal Thirst Responses to Systemic Hyperosmolality
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发表时间：
2006
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通讯作者：
S. Ciura;C. Bourque
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作者：
S. Ciura;C. Bourque
最近的研究表明，瞬时受体电位香草酸（TRPV）家族的阳离子通道的成员是正常的神经递质调节反应的产生所必需的，但在中枢神经系统的初级神经递质受体神经元的神经递质感觉转导的机制仍有待确定。事实上，尽管有充分的证据表明，血管器终板（OVLT）作为主要的位点的大脑渗透刺激的检测，证据表明，在OVLT的神经元本质上是神经元敏感性仍然难以捉摸。在这里，我们表明，小鼠OVLT神经元本质上是敏感的细胞外液的渗透压增加。高渗条件引起膜阳离子电导增加，导致产生内向电流，去极化受体电位和增强的动作电位放电。此外，我们还发现TRPV 1基因敲除小鼠OVLT神经元中不存在这种感觉信号转导级联，野生型OVLT神经元的反应可被TRPV通道抑制剂钌红阻断。最后，与WT对照组相比，TRPV 1/小鼠对全身性高渗反应的水摄入量显着减弱。这些研究结果表明，OVLT神经元作为主要的神经递质受体和trpv 1基因的产物是神经递质感觉转导所必需的。
Recent studies have indicated that members of the transient receptor potential vanilloid (TRPV) family of cation channels are required for the generation of normal osmoregulatory responses, yet the mechanism of osmosensory transduction in primary osmoreceptor neurons of the CNS remains to be defined. Indeed, despite ample evidence suggesting that the organum vasculosum lamina terminalis (OVLT) serves as the primary locus of the brain for the detection of osmotic stimuli, evidence that neurons in the OVLT are intrinsically osmosensitive has remained elusive. Here we show that murine OVLT neurons are intrinsically sensitive to increases in the osmolality of the extracellular fluid. Hypertonic conditions provoked increases in membrane cation conductance that resulted in the generation of an inward current, depolarizing osmoreceptor potentials, and enhanced action potential discharge. Moreover, we found that this osmosensory signal transduction cascade was absent in OVLT neurons from TRPV1 knock-out (TRPV1 / ) mice and that responses of wild type (WT) OVLT neurons could be blocked by ruthenium red, an inhibitor of TRPV channels. Finally, TRPV1 / mice showed significantly attenuated water intake in response to systemic hypertonicity compared with WT controls. These findings indicate that OVLT neurons act as primary osmoreceptors and that a product of the trpv1 gene is required for osmosensory transduction.