Nitric Oxide-Dependent Feedback Loop Regulates Transient Receptor Potential Vanilloid 4 (TRPV4) Channel Cooperativity and Endothelial Function in Small Pulmonary Arteriesopen access
- Authors
- Marziano, Corina; Hong, Kwangseok; Cope, Eric L.; Kotlikoff, Michael I.; Isakson, Brant E.; Sonkusare, Swapnil K.
- Issue Date
- Dec-2017
- Publisher
- WILEY
- Keywords
- calcium channel; calcium signaling; endothelial nitric oxide synthase; endothelium; microcirculation; pulmonary artery; signaling pathways; transient receptor potential vanilloid 4 channel; vascular endothelial function
- Citation
- JOURNAL OF THE AMERICAN HEART ASSOCIATION, v.6, no.12
- Journal Title
- JOURNAL OF THE AMERICAN HEART ASSOCIATION
- Volume
- 6
- Number
- 12
- URI
- https://scholarworks.bwise.kr/cau/handle/2019.sw.cau/45461
- DOI
- 10.1161/JAHA.117.007157
- ISSN
- 2047-9980
- Abstract
- Background-Recent studies demonstrate that spatially restricted, local Ca2+ signals are key regulators of endothelium-dependent vasodilation in systemic circulation. There are drastic functional differences between pulmonary arteries (PAs) and systemic arteries, but the local Ca2+ signals that control endothelium-dependent vasodilation of PAs are not known. Localized, unitary Ca2+ influx events through transient receptor potential vanilloid 4 (TRPV4) channels, termed TRPV4 sparklets, regulate endothelium-dependent vasodilation in resistance-sized mesenteric arteries via activation of Ca2+-dependent K+ channels. The objective of this study was to determine the unique functional roles, signaling targets, and endogenous regulators of TRPV4 sparklets in resistance-sized PAs. Methods and Results-Using confocal imaging, custom image analysis, and pressure myography in fourth-order PAs in conjunction with knockout mouse models, we report a novel Ca2+ signaling mechanism that regulates endothelium-dependent vasodilation in resistance-sized PAs. TRPV4 sparklets exhibit distinct spatial localization in PAs when compared with mesenteric arteries, and preferentially activate endothelial nitric oxide synthase (eNOS). Nitric oxide released by TRPV4-endothelial nitric oxide synthase signaling not only promotes vasodilation, but also initiates a guanylyl cyclase-protein kinase G-dependent negative feedback loop that inhibits cooperative openings of TRPV4 channels, thus limiting sparklet activity. Moreover, we discovered that adenosine triphosphate dilates PAs through a P2 purinergic receptor-dependent activation of TRPV4 sparklets. Conclusions-Our results reveal a spatially distinct TRPV4-endothelial nitric oxide synthase signaling mechanism and its novel endogenous regulators in resistance-sized PAs.
- Files in This Item
-
- Appears in
Collections - College of Education > Department of Physical Education > 1. Journal Articles
![qrcode](https://api.qrserver.com/v1/create-qr-code/?size=55x55&data=https://scholarworks.bwise.kr/cau/handle/2019.sw.cau/45461)
Items in ScholarWorks are protected by copyright, with all rights reserved, unless otherwise indicated.