Fig. 1

SARS-CoV-2 spike protein receptor-binding domain (S-RBD) induces an acute-to-prolonged perturbation of the intracellular calcium homeostasis in human pulmonary arterial endothelial cells (PAECs). a Schematic representation of the in vitro cell experimental design. b–g Representative traces and summarized data showing the effects of S-RBD (4 μg/mL for 1- and 2-hour) on intracellular calcium release induced by cyclopiazonic acid (CPA, 10 μM) and CPA-evoked store-operated calcium entry (SOCE) (b, c), baseline calcium and Piezo1 activity induced by agonist Yoda1 (0.5 μM) (d, e), TRPV4 activity induced by agonist GSK1016790A (GSK, 10 nM) (f, g) in cultured human PAECs. Bar values are mean ± SD, n = 5–7 experiments in 251 (IgG control, IgG), 213 (S-RBD 1 h) and 215 (S-RBD 2 h) cells for CPA-induced calcium release and SOCE, Yoda1-induced calcium response and baseline calcium measurements. Bar values are mean ± SD, n = 5–7 experiments in 269 (IgG control, IgG), 243 (S-RBD 1 h) and 229 (S-RBD 2 h) cells for GSK-induced calcium response. ^*P < 0.05, ^**P < 0.01 as indicated. h–m Representative traces and summarized data showing the effects of S-RBD (4 μg/mL for 24- and 72-hour) on intracellular calcium release induced by CPA (10 μM) and CPA-evoked SOCE (h, i), baseline calcium and Yoda1 (0.5 μM)-induced calcium increase (j, k), and GSK (10 nM)-induced calcium increase (l, m) in cultured human PAECs. Bar values are mean ± SD, n = 9–14 experiments in 344 (IgG 24 h), 401 (IgG 72 h), 321 (S-RBD 24 h) and 402 (S-RBD 72 h) cells for calcium release and SOCE measurements. Bar values are mean ± SD, n = 8–13 experiments in 357 (IgG 24 h), 322 (IgG 72 h), 341 (S-RBD 24 h) and 419 (S-RBD 72 h) cells for Yoda1 and baseline calcium measurements. Bar values are mean ± SD, n = 3-6 experiments in 240 (IgG 24 h), 169 (IgG 72 h), 158 (S-RBD 24 h) and 145 (S-RBD 72 h) cells for GSK measurements. ^*P < 0.05 as indicated