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Greenberg, Harry Z. E., Carlton-Carew, Simonette R. E., Khan, Dhanak M., Zargaran, Alexander K., Jahan, Kazi S., Ho, W.-S. Vanessa and Albert, Anthony P. 
ORCID: https://orcid.org/0000-0002-3596-9634
(2017)
Heteromeric TRPV4/TRPC1 channels mediate calcium-sensing receptor-induced nitric oxide production and vasorelaxation in rabbit mesenteric arteries.
Vascular Pharmacology, 96-98.
pp. 53-62.
ISSN 1537-1891
Abstract
Stimulation of calcium-sensing receptors (CaSR) by increasing the external calcium concentration (Ca2 +]o) induces endothelium-dependent vasorelaxation through nitric oxide (NO) production and activation of intermediate Ca2 +-activated K+ currents (IKCa) channels in rabbit mesenteric arteries. The present study investigates the potential role of heteromeric TRPV4-TRPC1 channels in mediating these CaSR-induced vascular responses. Immunocytochemical and proximity ligation assays showed that TRPV4 and TRPC1 proteins were expressed and co-localised at the plasma membrane of freshly isolated endothelial cells (ECs). In wire myography studies, increasing [Ca2 +]o between 1 and 6 mM induced concentration-dependent relaxations of methoxamine (MO)-induced pre-contracted tone, which were inhibited by the TRPV4 antagonists RN1734 and HC067047, and the externally-acting TRPC1 blocking antibody T1E3. In addition, CaSR-evoked NO production in ECs measured using the fluorescent NO indicator DAF-FM was reduced by RN1734 and T1E3. In contrast, [Ca2 +]o-evoked perforated-patch IKCa currents in ECs were unaffected by RN1734 and T1E3. The TRPV4 agonist GSK1016790A (GSK) induced endothelium-dependent relaxation of MO-evoked pre-contracted tone and increased NO production, which were inhibited by the NO synthase inhibitor L-NAME, RN1734 and T1E3. GSK activated 6pS cation channel activity in cell-attached patches from ECs which was blocked by RN1734 and T1E3. These findings indicate that heteromeric TRPV4-TRPC1 channels mediate CaSR-induced vasorelaxation through NO production but not IKCa channel activation in rabbit mesenteric arteries. This further implicates CaSR-induced pathways and heteromeric TRPV4-TRPC1 channels in regulating 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); and by the Biotechnology and Biological Sciences Research Council ( BB/J007226/1 to A.P.A). |
| Uncontrolled Keywords: | physiology,molecular medicine,pharmacology ,/dk/atira/pure/subjectarea/asjc/1300/1314 |
| 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: | 03 Nov 2024 07:30 |
| URI: | https://ueaeprints.uea.ac.uk/id/eprint/97245 |
| DOI: | 10.1016/j.vph.2017.08.005 |
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