The Molecular and Cellular Identity of Peripheral Osmoreceptors

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 trigge...

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Published in	Neuron (Cambridge, Mass.) Vol. 69; no. 2; pp. 332 - 344
Main Authors	Lechner, Stefan G., Markworth, Sören, Poole, Kate, Smith, Ewan St. John, Lapatsina, Liudmilla, Frahm, Silke, May, Marcus, Pischke, Sven, Suzuki, Makoto, Ibañez-Tallon, Inés, Luft, Friedrich C., Jordan, Jens, Lewin, Gary R.
Format	Journal Article
Language	English
Published	United States Elsevier Inc 27.01.2011 Elsevier Limited
Subjects	Animals Calcium - metabolism Cells, Cultured Chemoreceptor Cells - cytology Chemoreceptor Cells - physiology Drinking Extracellular Fluid - chemistry Ganglia, Spinal - cytology Gene expression Homeostasis Humans Kinases Liver - blood supply Liver - chemistry Mice Mice, Inbred C57BL Mice, Knockout Nervous system Neurons Neurons, Afferent - cytology Neurons, Afferent - physiology Osmolar Concentration Patch-Clamp Techniques Phorbols - metabolism Proteins Rodents Thermogenesis TRPV Cation Channels - antagonists & inhibitors TRPV Cation Channels - genetics TRPV Cation Channels - metabolism Veins & arteries Water-Electrolyte Balance - physiology Jordan (country)
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Abstract	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 (∼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. ► Liver sensory neuron osmotic changes following normal water intake ► Liver sensory neurons are osmoreceptive and located in the thoracic DRG ► Liver osmoreceptors transduce small hypo-osmotic shifts (∼20 mOsm) ► Osmoreceptor transduction requires the trp channel TRPV4
AbstractList	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 (~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.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 (~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. 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 (~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. 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 (∼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. ► Liver sensory neuron osmotic changes following normal water intake ► Liver sensory neurons are osmoreceptive and located in the thoracic DRG ► Liver osmoreceptors transduce small hypo-osmotic shifts (∼20 mOsm) ► Osmoreceptor transduction requires the trp channel TRPV4 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 (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. Highlights: Liver sensory neuron osmotic changes following normal water intake Liver sensory neurons are osmoreceptive and located in the thoracic DRG Liver osmoreceptors transduce small hypo-osmotic shifts (20 mOsm) Osmoreceptor transduction requires the trp channel TRPV4
Author	Suzuki, Makoto Lewin, Gary R. Poole, Kate Pischke, Sven Markworth, Sören Smith, Ewan St. John Lapatsina, Liudmilla Luft, Friedrich C. Jordan, Jens Lechner, Stefan G. Frahm, Silke May, Marcus Ibañez-Tallon, Inés
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Snippet	In mammals, the osmolality of the extracellular fluid (ECF) is highly stable despite radical changes in salt/water intake and excretion. Afferent systems are...
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SubjectTerms	Animals Calcium - metabolism Cells, Cultured Chemoreceptor Cells - cytology Chemoreceptor Cells - physiology Drinking Extracellular Fluid - chemistry Ganglia, Spinal - cytology Gene expression Homeostasis Humans Kinases Liver - blood supply Liver - chemistry Mice Mice, Inbred C57BL Mice, Knockout Nervous system Neurons Neurons, Afferent - cytology Neurons, Afferent - physiology Osmolar Concentration Patch-Clamp Techniques Phorbols - metabolism Proteins Rodents Thermogenesis TRPV Cation Channels - antagonists & inhibitors TRPV Cation Channels - genetics TRPV Cation Channels - metabolism Veins & arteries Water-Electrolyte Balance - physiology
Title	The Molecular and Cellular Identity of Peripheral Osmoreceptors
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