A Verma

AK Johnson

AP Sinke

B Kinsman

BJ Oldfield

CW Bourque

G Egan

GG Haddad

H Morita

H Tsushima

J Xu

JJ Zhou

JM Moreau

KA Hossmann

KR Westerterp

L Ma

MA Osundiji

MD Maines

MI Surks

MJ McKinley

MT Borra

RC Jung

RJ Chen

RM Jones

S Ciura

SE Williams

SF Pedersen

SG Lechner

SV Conde

TL Leal

W Liedtke

X Gao

Y Xia

Scientific Reports

AbstractThe phenomenon of water intake reduction during the 1st day of hypobaric hypoxia has been known for a long time. However, the reason for the same is yet unknown. The transient receptor potential vanilloid (TRPV) channels, including TRPV1 and TRPV4, are located in the subfornical organ (SFO). These are calcium permeable cationic channels gated by various stimuli such as cell swelling, low pH, and high temperature, and participate in anti-dipsogenic effects when activated. We aimed to explore the drinking behavior of rats and the mechanism of TRPVs under hypoxia. Chemical TRPV4 inhibitors (HC-067047 and Gadolinium) or TRPV4 knockout, but not TRPV1 inhibitor SB-705498, could restore the water intake under hypoxia. Hypoxia-mediated direct activation of TRPV4 may be the reason of anti-dipsogenic effects because the serum sodium, pH, and intracranial temperature are unaltered. Interestingly, we found that hypoxia immediately increased the intracellular Ca2+ concentration ([Ca2+]i) in HEK293-TRPV4 cells and primary neurons from SFO region, but not in the HEK293-TRPV1 cells. Moreover, hypoxia-induced [Ca2+]i increase depended on the indispensable hemeoxygenase-2 (HO-2) and TRPV4. HO-2 and TRPV4 were also confirmed to form a complex in SFO neurons. These results demonstrated that SFO cells sense hypoxia and activate via the HO-2/TRPV4 multiple channels, which are associated with anti-dipsogenic effects.</jats:p

Fan Yang

Li Zhou

Dong Wang

Li-Li Yang

Guo-Rong Yuan

Qing-Yuan Huang

Crossref

Suppression of TRPV4 channels ameliorates anti-dipsogenic effects under hypoxia in the subfornical organ of rats

Suppression of TRPV4 channels ameliorates anti-dipsogenic effects under hypoxia in the subfornical organ of rats

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