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Acid Sensing Ion Channel 1 Contributes to Ca 2+ Influx in Endothelial Tubes from Small Mesenteric Resistance Arteries
Author(s) -
Garcia Selina M.,
Herbert Lindsay M.,
Naik Jay S.,
Resta Thomas C,
Jernigan Nikki L.
Publication year - 2017
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.31.1_supplement.689.11
Subject(s) - vasodilation , mesenteric arteries , vasoconstriction , chemistry , medicine , endocrinology , biophysics , biology , artery
Our laboratory has previously shown that acid sensing ion channel 1 (ASIC1) is expressed in pulmonary arterial smooth muscle and contributes to agonist‐induced Ca 2+ influx and vasoconstriction secondary to depletion of intracellular Ca 2+ stores. In contrast to the vasoconstrictor role of ASIC1 in the pulmonary circulation; in mesenteric arteries, ASIC1 participates in acetylcholine (ACh)‐induced vasodilation. We hypothesized that ACh activates ASIC1‐mediated mesenteric endothelial cell Ca 2+ influx through a store‐operated mechanism. To test this hypothesis, we freshly isolated endothelial tubes from small mesenteric resistance arteries (100–200 mm inner diameter). To specifically examine ASIC1‐mediated endothelial cell Ca 2+ influx, independent of Ca 2+ release from stores, we assessed Mn 2+ ‐quenching of fura‐2 fluorescence in the presence or absence of the specific ASIC1 antagonist, psalmotoxin 1 (PcTX1; 20 nM). Whereas PcTX1 significantly diminished ACh (1 mM)‐induced Ca 2+ influx, ASIC1 inhibition was without effect on Ca 2+ entry in response to store depletion with cyclopiazonic acid (CPA; 10 μM). We conclude that ASIC1 contributes to ACh‐induced Ca 2+ influx in mesenteric endothelial cells; however, this response does not appear to be mediated through a store‐operated mechanism. Future studies will examine the mechanism(s) of receptor‐mediated ASIC1 activation in endothelial cells, as well as potential downstream targets leading to endothelium‐dependent vasodilation. 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), R01 HL132883 (to T.C. Resta), and AHA 16GRNT27700010 (to T.C. Resta).