Impaired pressure sensation in mice lacking TRPV4.
The sensation of pressure, mechanosensation, in vertebrates remains poorly understood on the molecular level. The ion channel TRPV4 is in the TRP family and is a candidate for a mechanosensitive calcium-permeable channel. It is located in dorsal root ganglia. In the present study, we show that disrupting the Trpv4 gene in mice markedly reduced the sensitivity of the tail to pressure and acidic nociception. The threshold to noxious stimuli and the conduction velocity of myelinated nerve responding to stimuli were also impaired. Activation of unmyelinated nerve was undetected. However, the mouse still retained olfaction, taste sensation, and heat avoidance. The TRPV4 channel expressed in vitro in Chinese hamster ovary cells was opened by low pH, citrate, and inflation but not by heat or capsaicin. These data identify the TRPV4 channel as essential for the normal detection of pressure and as a receptor of the high-threshold mechanosensory complex.
Suzuki
Makoto
M
Department of Pharmacology, Jichi Medical School, 3311-1 Yakushiji, Minamikawachi, Tochigi 329-0498, Japan.
Mizuno
Atsuko
A
Kodaira
Kunihiko
K
Imai
Masashi
M
D000818:Animals; D015152:Blotting, Northern; D016466:CHO Cells; D027682:Cation Transport Proteins; D006224:Cricetinae; D005727:Ganglia, Spinal / Q000502:physiology*; D007473:Ion Channels / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D007668:Kidney / Q000502:physiology; D008465:Mechanoreceptors / Q000502:physiology*; D008564:Membrane Potentials / Q000502:physiology; D051379:Mice; D018345:Mice, Knockout; D008969:Molecular Sequence Data; D009474:Neurons / Q000502:physiology*; D009997:Osmotic Pressure; D012677:Sensation / Q000502:physiology*; D050916:TRPV Cation Channels; D014162:Transfection
D027682:Cation Transport Proteins; D007473:Ion Channels; D050916:TRPV Cation Channels; C486576:Trpv4 protein, mouse