Endoplasmic reticulum stress induces sarco/endoplasmic reticulum calcium ATPase and alters calcium homeostasis in the vasculature

Calcium homeostasis is tightly regulated in the vasculature. The sarco/endoplasmic reticulum (ER) Ca2+‐ATPase (SERCA) is responsible for maintaining a relatively low cytosolic Ca2+ concentration. The ER is a multifunctional organelle and is easily perturbed resulting in ER stress. When ER stress occurs, the ER initiates a cellular signaling network, the unfolded protein response (UPR) to alleviate this stress. We tested the hypothesis that during ER stress increased SERCA function would lead to increased Ca2+‐induced contraction and elevated ER Ca2+ stores in the aorta of male mice. Male CD‐1 mice were treated with tunicamycin (TM, 100mg/kg, 8hrs, i.p.), an inducer of ER stress or vehicle (saline, 125ul, 8hrs, i.p.). TM treatment significantly upregulated aortic SERCA2b expression. Using a wire myograph, aortic rings of TM treated mice had an increased Ca2+‐induced contraction when compared to control (99.7%±2.6% vs. 69.4%±2.7%) in the presence of thapsigargin (TG, 1μM), an inhibitor of SERCA. Caffeine (10mM) induced depletion of intracellular Ca2+ stores measured as a transient contraction, was greater in aortic rings from TM treated mice (62.1%±5.1% vs. 44.1%±3.9%) compared to controls which was completely abolished in the presence of TG (6.8%±1.7% vs 7.4%±1.1%). Therefore augmented SERCA activity following ER stress may be a mechanisms altering Ca2+ homeostasis in the vasculature.