Suppression of TRPV4 channels ameliorates anti-dipsogenic effects under hypoxia in the subfornical organ of rats
| Autor: | Li Zhou, Fan Yang, Dong Wang, Guo-Rong Yuan, Qing-Yuan Huang, Li-Li Yang |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2016 |
| Předmět: |
Male
0301 basic medicine TRPV4 medicine.medical_specialty Pyrrolidines Morpholines Drinking TRPV1 TRPV Cation Channels chemistry.chemical_element Gadolinium Calcium Biology TRPV Article Cell Line Rats Sprague-Dawley 03 medical and health sciences Transient receptor potential channel 0302 clinical medicine Internal medicine medicine Animals Humans Urea Pyrroles Hypoxia Neurons Calcium metabolism Multidisciplinary Sodium Temperature Hydrogen-Ion Concentration Hypoxia (medical) Subfornical organ Rats HEK293 Cells 030104 developmental biology Endocrinology medicine.anatomical_structure chemistry Heme Oxygenase (Decyclizing) medicine.symptom 030217 neurology & neurosurgery Subfornical Organ |
| Zdroj: | Scientific Reports |
| ISSN: | 2045-2322 |
| DOI: | 10.1038/srep30168 |
| Popis: | The 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. |
| Databáze: | OpenAIRE |
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