Impaired osmotic sensation in mice lacking TRPV4.
The Ca2+-permeable cation channel TRPV4, which is part of the Trp family located in the circumventricular organs, is activated by cell swelling. To investigate the role of TRPV4 in osmotic sensation, we disrupted the TRPV4 gene in mice and examined the effect on osmotic metabolism. Disruption of the mouse TRPV4 gene did not influence either water intake behavior or serum osmolality. Short-term salt ingestion, however, seemed to impair the transient free water clearance. The level of serum arginine vasopressin (AVP) of TRPV4-/- mice was not significantly changed under normal conditions but was significantly increased under stimulated conditions. Incubation of brain slices with graded hyperosmolality suggested an exaggerated response of AVP secretion in TRPV4-/- mice. Thus TRPV4 in the brain may transmit a negative signal to AVP secretion similar to an inhibitory pass through the baroregulatory system. Thus, in the regulation of serum osmolality, TRPV4 is a swell-activated channel that appears to play a role in reversion toward hyposmolality.
Mizuno
Atsuko
A
Department of Pharmacology, Jichi Medical School, Minamikawachi, Tochigi, 329-0498, Japan.
Matsumoto
Naoko
N
Imai
Masashi
M
Suzuki
Makoto
M
D000818:Animals; D001127:Arginine Vasopressin / Q000097:blood / Q000378:metabolism; D001921:Brain / Q000378:metabolism; D015220:Calcium Channels / Q000378:metabolism; D027682:Cation Transport Proteins; D004326:Drinking / Q000502:physiology; D005260:Female; D007473:Ion Channels / Q000235:genetics*; D008297:Male; D008465:Mechanoreceptors / Q000502:physiology; D051379:Mice; D018345:Mice, Knockout; D009924:Organ Culture Techniques; D009997:Osmotic Pressure; D012965:Sodium Chloride / Q000494:pharmacology; D050916:TRPV Cation Channels; D014882:Water-Electrolyte Balance / Q000502:physiology*
D015220:Calcium Channels; D027682:Cation Transport Proteins; D007473:Ion Channels; D050916:TRPV Cation Channels; C486576:Trpv4 protein, mouse; D001127:Arginine Vasopressin; D012965:Sodium Chloride