T-type voltage gated calcium channels are involved in endothelium-dependent relaxation of mice pulmonary artery

Abstract : In pulmonary arterial endothelial cells, Ca2+ channels and intracellular Ca2+ concentration ([Ca2+]i) control the release of vasorelaxant factors such as nitric oxide and are involved in the regulation of pulmonary arterial blood pressure. The present study was undertaken to investigate the implication of T-type voltage-gated Ca2+ channels (T-VGCCs, Cav3.1 channel) in the endothelium-dependent relaxation of intrapulmonary arteries. Relaxation was quantified by means of a myograph in wild type and Cav3.1-/- mice. Endothelial [Ca2+]i and NO production were measured, on whole vessels, with the fluo-4 and DAF-fm probes. Acetylcholine (ACh) induced a nitric oxide- and endothelium-dependent relaxation that was significantly reduced in pulmonary arteries from Cav3.1-/- compared to wild type mice as well as in the presence of T-VGCC inhibitors (NNC 55-0396 or mibefradil). ACh also increased endothelial [Ca2+]i and NO production that were both reduced in Cav3.1-/- compared to wild type mice or in the presence of T-VGCC inhibitors. Immunofluorescence labeling revealed the presence of Cav3.1 channels in endothelial cells that co-localized with endothelial nitric oxide synthase in arteries from wild type mice. TRPV4-, beta2 adrenergic- and nitric oxide donors (SNP)-mediated relaxation were not altered in Cav3.1-/- compared to wild type mice. Finally, in chronically hypoxic mice, a model of pulmonary hypertension, ACh relaxation was reduced but still depended on Cav3.1 channels activity. The present study thus demonstrates that T-VGCCs, mainly Cav3.1 channel, contribute to intrapulmonary vascular reactivity in mice by controlling endothelial [Ca2+]i and ACh-mediated relaxation.
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https://hal.umontpellier.fr/hal-02060440
Contributeur : Sandrine Beraud <>
Soumis le : jeudi 7 mars 2019 - 13:47:44
Dernière modification le : mardi 23 juillet 2019 - 09:30:03

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Guillaume Gilbert, Arnaud Courtois, Mathilde Dubois, Laure-Anne Cussac, Thomas Ducret, et al.. T-type voltage gated calcium channels are involved in endothelium-dependent relaxation of mice pulmonary artery. Biochemical Pharmacology, Elsevier, 2017, 138, pp.61-72. ⟨10.1016/j.bcp.2017.04.021⟩. ⟨hal-02060440⟩

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