title: Hypertonicity sensing in organum vasculosum lamina terminalis neurons: a mechanical process involving TRPV1 but not TRPV4.
abstract: Primary osmosensory neurons in the mouse organum vasculosum lamina terminalis (OVLT) transduce hypertonicity via the activation of nonselective cation channels that cause membrane depolarization and increased action potential discharge, and this effect is absent in mice lacking expression of the transient receptor potential vanilloid 1 (Trpv1) gene (Ciura and Bourque, 2006). However other experiments have indicated that channels encoded by Trpv4 also contribute to central osmosensation in mice (Liedtke and Friedman, 2003; Mizuno et al., 2003). At present, the mechanism by which hypertonicity modulates cation channels in OVLT neurons is unknown, and it remains unclear whether Trpv1 and Trpv4 both contribute to this process. Here, we show that physical shrinking is necessary and sufficient to mediate hypertonicity sensing in OVLT neurons isolated from adult mice. Steps coupling progressive decreases in cell volume to increased neuronal activity were quantitatively equivalent whether shrinking was evoked by osmotic pressure or mechanical aspiration. Finally, modulation of OVLT neurons by tonicity or mechanical stimulation was unaffected by deletion of trpv4 but was abolished in cells lacking Trpv1 or wild-type neurons treated with the TRPV1 antagonist SB366791. Thus, hypertonicity sensing is a mechanical process requiring Trpv1, but not Trpv4.
authors: Center for Research in Neuroscience, Research Institute of the McGill University Health Centre, Montreal General Hospital, Montreal, Quebec, H3G 1A4, Canada.
authors: Sorana
authors: S
authors: Ciura
authors: Wolfgang
authors: W
authors: Liedtke
authors: Charles W
authors: CW
authors: Bourque
mesh_terms: D000818:Animals; D001703:Biophysics; D002118:Calcium / Q000378:metabolism; D048429:Cell Size; D004558:Electric Stimulation; D005260:Female; D007031:Hypothalamus / Q000166:cytology*; D008297:Male; D040542:Mechanotransduction, Cellular / Q000235:genetics / Q000502:physiology*; D008564:Membrane Potentials / Q000235:genetics / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009474:Neurons / Q000502:physiology*; D009994:Osmolar Concentration; D018408:Patch-Clamp Techniques / Q000379:methods; D050916:TRPV Cation Channels / Q000172:deficiency / Q000378:metabolism*; D013997:Time Factors; D014882:Water-Electrolyte Balance / Q000502:physiology*
chemical_list: D050916:TRPV Cation Channels; C493921:TRPV1 protein, mouse; C486576:Trpv4 protein, mouse; D002118:Calcium