DeLalio, LJ;
Keller, AS;
Chen, J;
Boyce, AKJ;
Artamonov, MV;
Askew-Page, HR;
Keller, TCS;
Johnstone, SR;
Weaver, RB;
Good, ME;
et al.
DeLalio, LJ; Keller, AS; Chen, J; Boyce, AKJ; Artamonov, MV; Askew-Page, HR; Keller, TCS; Johnstone, SR; Weaver, RB; Good, ME; Murphy, SA; Best, AK; Mintz, EL; Penuela, S; Greenwood, IA; Machado, RF; Somlyo, AV; Swayne, LA; Minshall, RD; Isakson, BE
(2018)
Interaction Between Pannexin 1 and Caveolin-1 in Smooth Muscle Can Regulate Blood Pressure.
Arterioscler Thromb Vasc Biol, 38 (9).
pp. 2065-2078.
ISSN 1524-4636
https://doi.org/10.1161/ATVBAHA.118.311290
SGUL Authors: Greenwood, Iain Andrew
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Abstract
Objective- Sympathetic nerve innervation of vascular smooth muscle cells (VSMCs) is a major regulator of arteriolar vasoconstriction, vascular resistance, and blood pressure. Importantly, α-adrenergic receptor stimulation, which uniquely couples with Panx1 (pannexin 1) channel-mediated ATP release in resistance arteries, also requires localization to membrane caveolae. Here, we test whether localization of Panx1 to Cav1 (caveolin-1) promotes channel function (stimulus-dependent ATP release and adrenergic vasoconstriction) and is important for blood pressure homeostasis. Approach and Results- We use in vitro VSMC culture models, ex vivo resistance arteries, and a novel inducible VSMC-specific Cav1 knockout mouse to probe interactions between Panx1 and Cav1. We report that Panx1 and Cav1 colocalized on the VSMC plasma membrane of resistance arteries near sympathetic nerves in an adrenergic stimulus-dependent manner. Genetic deletion of Cav1 significantly blunts adrenergic-stimulated ATP release and vasoconstriction, with no direct influence on endothelium-dependent vasodilation or cardiac function. A significant reduction in mean arterial pressure (total=4 mm Hg; night=7 mm Hg) occurred in mice deficient for VSMC Cav1. These animals were resistant to further blood pressure lowering using a Panx1 peptide inhibitor Px1IL2P, which targets an intracellular loop region necessary for channel function. Conclusions- Translocalization of Panx1 to Cav1-enriched caveolae in VSMCs augments the release of purinergic stimuli necessary for proper adrenergic-mediated vasoconstriction and blood pressure homeostasis.
Item Type: |
Article
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Additional Information: |
This is a non-final version of an article published in final form in DeLalio, LJ; Keller, AS; Chen, J; Boyce, AKJ; Artamonov, MV; Askew-Page, HR; Keller, TCS; Johnstone, SR; Weaver, RB; Good, ME; et al. (2018) Interaction Between Pannexin 1 and Caveolin-1 in Smooth Muscle Can Regulate Blood Pressure. Arterioscler Thromb Vasc Biol, 38 (9). pp. 2065-2078. |
Keywords: |
Pannexin 1, adrenergic agents, blood pressure, caveolae, muscle, smooth, Adenosine Triphosphate, Adrenergic alpha-1 Receptor Agonists, Animals, Blood Pressure, Caveolin 1, Cell Membrane, Cells, Cultured, Connexins, Homeostasis, Humans, Male, Mice, Knockout, Muscle, Smooth, Vascular, Myocytes, Smooth Muscle, Nerve Tissue Proteins, Phenylephrine, Sympathetic Nervous System, Vasoconstriction, Muscle, Smooth, Vascular, Sympathetic Nervous System, Cells, Cultured, Cell Membrane, Myocytes, Smooth Muscle, Animals, Mice, Knockout, Humans, Phenylephrine, Connexins, Nerve Tissue Proteins, Adenosine Triphosphate, Homeostasis, Blood Pressure, Vasoconstriction, Male, Caveolin 1, Adrenergic alpha-1 Receptor Agonists, adrenergic agents, blood pressure, caveolae, muscle, smooth, Pannexin 1, Pannexin 1, adrenergic agents, blood pressure, caveolae, muscle, smooth, Cardiovascular System & Hematology, 1103 Clinical Sciences, 1102 Cardiorespiratory Medicine and Haematology |
SGUL Research Institute / Research Centre: |
Academic Structure > Molecular and Clinical Sciences Research Institute (MCS) |
Journal or Publication Title: |
Arterioscler Thromb Vasc Biol |
ISSN: |
1524-4636 |
Language: |
eng |
Dates: |
Date | Event |
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September 2018 | Published | 19 July 2018 | Published Online | 19 June 2018 | Accepted |
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Publisher License: |
Publisher's own licence |
Projects: |
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PubMed ID: |
30026274 |
Web of Science ID: |
WOS:000442507900012 |
![](http://static.pubmed.gov/portal/portal3rc.fcgi/2745237/img/27842) |
Go to PubMed abstract |
URI: |
https://openaccess.sgul.ac.uk/id/eprint/112718 |
Publisher's version: |
https://doi.org/10.1161/ATVBAHA.118.311290 |
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