Tools
Tools
Greenberg, Harry Z. E., Carlton-Carew, Simonette R. E., Zargaran, Alexander K., Jahan, Kazi S., Birnbaumer, Lutz and Albert, Anthony P. 
ORCID: https://orcid.org/0000-0002-3596-9634
(2019)
Heteromeric TRPV4/TRPC1 channels mediate calcium-sensing receptor-induced relaxations and nitric oxide production in mesenteric arteries: Comparative study using wild-type and TRPC1−/- mice.
Channels, 13 (1).
pp. 410-423.
ISSN 1933-6950
Abstract
We have previously provided pharmacological evidence that stimulation of calcium-sensing receptors (CaSR) induces endothelium-dependent relaxations of rabbit mesenteric arteries through activation of heteromeric TRPV4/TRPC1 channels and nitric oxide (NO) production. The present study further investigates the role of heteromeric TRPV4/TRPC1 channels in these CaSR-induced vascular responses by comparing responses in mesenteric arteries from wild-type (WT) and TRPC1-/- mice. In WT mice, stimulation of CaSR induced endothelium-dependent relaxations of pre-contracted tone and NO generation in endothelial cells (ECs), which were inhibited by the TRPV4 channel blocker RN1734 and the TRPC1 blocking antibody T1E3. In addition, TRPV4 and TRPC1 proteins were colocalised at, or close to, the plasma membrane of endothelial cells (ECs) from WT mice. In contrast, in TRPC1-/- mice, CaSR-mediated vasorelaxations and NO generation were greatly reduced, unaffected by T1E3, but blocked by RN1734. In addition, the TRPV4 agonist GSK1016790A (GSK) induced endothelium-dependent vasorelaxations which were blocked by RN1734 and T1E3 in WT mice, but only by RN1734 in TRPC1-/- mice. Moreover, GSK activated cation channel activity with a 6pS conductance in WT ECs but with a 52 pS conductance in TRPC1-/- ECs. These results indicate that stimulation of CaSR activates heteromeric TRPV4/TRPC1 channels and NO production in ECs, which are responsible for endothelium-dependent vasorelaxations. This study also suggests that heteromeric TRPV4-TRPC1 channels may form the predominant TRPV4-containing channels in mouse mesenteric artery ECs. Together, our data further implicates CaSR-induced pathways and heteromeric TRPV4/TRPC1 channels in the regulation of vascular tone.
| Item Type: | Article |
|---|---|
| Additional Information: | Funding Information: This work was supported by a British Heart Foundation PhD Studentship for H.Z.E. Greenberg [FS/13/10/30021 to A.P.A]; by the Biotechnology and Biological Sciences Research Council [BB/J007226/1 and BB/M018350/1 to APA]; and in part by the NIH Intramural Research Program [Project Z01-ES-101684 to L.B]. |
| Uncontrolled Keywords: | calcium-sensing receptors,endothelium,nitric oxide,trpc1,trpv4,vascular smooth muscle,biophysics,biochemistry ,/dk/atira/pure/subjectarea/asjc/1300/1304 |
| Faculty \ School: | Faculty of Medicine and Health Sciences > Norwich Medical School |
| Related URLs: | |
| Depositing User: | LivePure Connector |
| Date Deposited: | 29 Oct 2024 09:30 |
| Last Modified: | 12 Nov 2024 14:30 |
| URI: | https://ueaeprints.uea.ac.uk/id/eprint/97244 |
| DOI: | 10.1080/19336950.2019.1673131 |
Actions (login required)
 |
View Item |