The Molecular and Cellular Identity of Peripheral Osmoreceptors
The Molecular and Cellular Identity of Peripheral Osmoreceptors
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DOI：
10.1016/j.neuron.2010.12.028
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发表时间：
2011-01-27
期刊：
影响因子：
16.2
通讯作者：
Lewin, Gary R.
中科院分区：
文献类型：
--
作者：
Lechner, Stefan G.;Markworth, Soeren;Lewin, Gary R.
在哺乳动物中，尽管盐/水的摄入和排泄发生了根本变化，但细胞外液（ECF）的渗透压仍然高度稳定。传入系统需要检测 ECF 中的低渗或高渗变化，以触发渗透压的稳态控制。在人类中，升压反射是由简单的饮用水引发的，这可能是由外周渗透压感受器介导的。在这里，我们鉴定了小鼠胸背根神经节（DRG）中的传入神经元，它们支配肝血管并检测血液渗透压的生理性低渗变化。肝脏感觉神经元配备有内向电流，可忠实地转换生理范围内渗透压的分级变化（类似于 15 mOsm）。在缺乏渗透激活离子通道 TRPV4 的小鼠中，肝脏感觉神经元不再表现出渗透敏感的内向电流，并且体内外周渗透压感受器的激活被消除。因此，我们发现了一群新的感觉神经元，它们可以传导肝脏渗透压的持续变化。
In mammals, the osmolality of the extracellular fluid (ECF) is highly stable despite radical changes in salt/water intake and excretion. Afferent systems are required to detect hypo- or hyperosmotic shifts in the ECF to trigger homeostatic control of osmolality. In humans, a pressor reflex is triggered by simply drinking water which may be mediated by peripheral osmoreceptors. Here, we identified afferent neurons in the thoracic dorsal root ganglia (DRG) of mice that innervate hepatic blood vessels and detect physiological hypo-osmotic shifts in blood osmolality. Hepatic sensory neurons are equipped with an inward current that faithfully transduces graded changes in osmolality within the physiological range (similar to 15 mOsm). In mice lacking the osmotically activated ion channel, TRPV4, hepatic sensory neurons no longer exhibit osmosensitive inward currents and activation of peripheral osmoreceptors in vivo is abolished. We have thus identified a new population of sensory neurons that transduce ongoing changes in hepatic osmolality.