Coupling of store-operated calcium entry to vasoconstriction is acid-sensing ion channel 1a dependent in pulmonary but not mesenteric arteries

Selina M Garcia, Lindsay M Herbert, Benjimen R Walker, Thomas C Resta, Nikki L Jernigan
PloS One 2020, 15 (7): e0236288
Although voltage-gated Ca2+ channels (VGCC) are a major Ca2+ entry pathway in vascular smooth muscle cells (VSMCs), several other Ca2+-influx mechanisms exist and play important roles in vasoreactivity. One of these is store-operated Ca2+ entry (SOCE), mediated by an interaction between STIM1 and Orai1. Although SOCE is an important mechanism of Ca2+ influx in non-excitable cells (cells that lack VGCC); there is debate regarding the contribution of SOCE to regulate VSMC contractility and the molecular components involved. Our previous data suggest acid-sensing ion channel 1a (ASIC1a) is a necessary component of SOCE and vasoconstriction in small pulmonary arteries. However, it is unclear if ASIC1a similarly contributes to SOCE and vascular reactivity in systemic arteries. Considering the established role of Orai1 in mediating SOCE in the systemic circulation, we hypothesize the involvement of ASIC1a in SOCE and resultant vasoconstriction is unique to the pulmonary circulation. To test this hypothesis, we examined the roles of Orai1 and ASIC1a in SOCE- and endothelin-1 (ET-1)-induced vasoconstriction in small pulmonary and mesenteric arteries. We found SOCE is coupled to vasoconstriction in pulmonary arteries but not mesenteric arteries. In pulmonary arteries, inhibition of ASIC1a but not Orai1 attenuated SOCE- and ET-1-induced vasoconstriction. However, neither inhibition of ASIC1a nor Orai1 altered ET-1-induced vasoconstriction in mesenteric arteries. We conclude that SOCE plays an important role in pulmonary, but not mesenteric, vascular reactivity. Furthermore, in contrast to the established role of Orai1 in SOCE in non-excitable cells, the SOCE response in pulmonary VSMCs is largely mediated by ASIC1a.

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