Rationale: Exposure to acute hypoxia causes vasoconstriction in both pulmonary arteries (PA) and pulmonary veins (PV). The mechanisms on the arterial side have been studied extensively. However, bare attention has been paid to the venous side.
Objectives: To investigate if acute hypoxia caused the increase of intracellular Ca(2+) concentration ([Ca(2+)]i), and Ca(2+) influx through store-operated calcium channels (SOCC) in pulmonary venous smooth muscle cells (PVSMCs).
Methods: Fluorescent microscopy and fura-2 were used to measure effects of 4% O2 on [Ca(2+)]i and store-operated Ca(2+) entry (SOCE) in isolated rat distal PVSMCs.
Measurements and main results: In PVSMCs perfused with Ca(2+)-free Krebs Ringer bicarbonate solution (KRBS) containing cyclopiazonic acid to deplete Ca(2+) stores in the sarcoplasmic reticulum (SR) and nifedipine to prevent Ca(2+) entry through L-type voltage-depended Ca(2+) channels (VDCC), hypoxia markedly enhanced both the increase in [Ca(2+)]i caused by restoration of extracellular [Ca(2+)] and the rate at which extracellular Mn(2+) quenched fura-2 fluorescence. Moreover, the increased [Ca(2+)]i in PVSMCs perfused with normal salt solution was completely blocked by SOCC antagonists SKF-96365 and NiCl2 at concentrations that SOCE >85% was inhibited but [Ca(2+)]i responses to 60 mM KCl were not altered. On the contrary, L-type VDCC antagonist nifedipine inhibited increase in [Ca(2+)]i to hypoxia by only 50% at concentrations that completely blocked responses to KCl. The increased [Ca(2+)]i caused by hypoxia was completely abolished by perfusion with Ca(2+)-free KRBS.
Conclusions: These results suggest that acute hypoxia enhances SOCE via activating SOCCs, leading to increased [Ca(2+)]i in distal PVSMCs.
Keywords: Calcium signaling; intracellular Ca2+ concentration ([Ca2+]i); pulmonary venous smooth muscle (PVSM); store-operated Ca2+ entry (SOCE).