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 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.
Department of Neuroscience, Max-Delbrück Center for Molecular Medicine, Robert-Rössle-Straße 10, D-13092 Berlin-Buch, Germany.
Stefan G
SG
Lechner
Sören
S
Markworth
Kate
K
Poole
Ewan St John
ES
Smith
Liudmilla
L
Lapatsina
Silke
S
Frahm
Marcus
M
May
Sven
S
Pischke
Makoto
M
Suzuki
Inés
I
Ibañez-Tallon
Friedrich C
FC
Luft
Jens
J
Jordan
Gary R
GR
Lewin
D000818:Animals; D002118:Calcium / Q000378:metabolism; D002478:Cells, Cultured; D002628:Chemoreceptor Cells / Q000166:cytology / Q000502:physiology*; D004326:Drinking; D045604:Extracellular Fluid / Q000737:chemistry*; D005727:Ganglia, Spinal / Q000166:cytology; D006706:Homeostasis; D006801:Humans; D008099:Liver / Q000098:blood supply / Q000737:chemistry; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009475:Neurons, Afferent / Q000166:cytology / Q000502:physiology*; D009994:Osmolar Concentration; D018408:Patch-Clamp Techniques; D010704:Phorbols / Q000378:metabolism; D050916:TRPV Cation Channels / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D014882:Water-Electrolyte Balance / Q000502:physiology
C517592:4alpha-phorbol 12,13-didecanone; D010704:Phorbols; D050916:TRPV Cation Channels; C486576:Trpv4 protein, mouse; D002118:Calcium