Premium
Stimulation of Muscarinic Receptors Activate Acid Sensing Ion Channel 1 in Isolated Mesenteric Artery Endothelial Tubes
Author(s) -
Garcia Selina M,
Herbert Lindsay M,
Naik Jay S,
Resta Thomas C,
Jernigan Nikki L
Publication year - 2019
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.2019.33.1_supplement.827.9
Subject(s) - mesenteric arteries , arachidonic acid , vasodilation , vasoconstriction , acetylcholine , vascular smooth muscle , medicine , microbiology and biotechnology , endocrinology , chemistry , biology , biochemistry , artery , smooth muscle , enzyme
Acid sensing ion channel 1 (ASIC1) belongs to the amiloride‐sensitive degenerin/epithelial sodium channel superfamily and is permeable to both Na + and Ca 2+ . ASIC1 is expressed in vascular smooth muscle and/or endothelial cells of various vascular beds and is activated following stimulation of G protein‐coupled receptors (GPCR). In the pulmonary circulation, ASIC1 contributes to GPCR‐induced vasoconstriction and vascular smooth muscle Ca 2+ influx via a store‐operated Ca 2+ entry (SOCE) mechanism. In small mesenteric arteries, we have recently shown that ASIC1 contributes to acetylcholine (ACh)‐induced vasodilation and endothelial cell Ca 2+ entry, however ASIC1‐mediated Ca 2+ influx is not SOCE‐dependent in mesenteric artery endothelial cells. Thus, further investigation is needed to understand the mechanism by which ASIC1 is activated by GPCR in small mesenteric artery endothelial cells. Previous studies show ASIC1 is activated by arachidonic acid, therefore we hypothesized that acetylcholine stimulates ASIC1 in mesenteric artery endothelial cells through activation of phospholipase A 2 (PLA 2 ) and release of arachidonic acid. To test this hypothesis, we examined endothelial Ca 2+ influx via Mn 2+ quenching of fura‐2 fluorescence in freshly isolated mesenteric artery endothelial tubes. The PLA inhibitor methyl arachidonyl fluorophosphonate (MAF; 500 nM) attenuated the Ca 2+ entry response to ACh, confirming that PLA 2 ‐signaling contributes to the ACh‐induced Ca 2+ entry in mesenteric artery endothelial cells. In addition, the selective inhibitor of ASIC1, psalmotoxin 1 (PcTX1; 20 nM), attenuated arachidonic acid‐induced Ca 2+ ‐influx in mesenteric artery endothelial tubes. Although these studies suggest stimulation of muscarinic receptors activate ASIC1 through a PLA 2 ‐arachidonic acid signaling mechanism in mesenteric endothelium, further studies are needed to identify the downstream effector of ASIC1. Support or Funding Information Supported by National Heart, Lung, and Blood Institute Grants R01 HL‐111084 (to N.L. Jernigan), T32 HL007736 (to T.C. Resta), and American Heart Association Grant 18TPA34110281 (to N.L. Jernigan). This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .