Effect of Acute Hypoxia on Cyclopiazonic Acid Induced Intracellular Calcium Cation Enhancement in Rat Distal Pulmonary Venous Smooth Muscle Cells

Objective: To study the effect and the mechanism of acute hypoxia on Ca2+-ATPase inhibitor, cyclopiazonic acid(CPA) induced intracellular calcium cation enhancement in rat distal pulmonary venous smooth muscle cells(PVSMC). Methods: The PVSMC were isolated from 6 male SD rats and the cells were cultured for further experiment. Enhancing effects of CPA, acute hypoxia(4% O2) on [Ca2+]i in distal PVSMC and the interventional effects of 2 store-operated Ca2+ channels(SOCC) inhibitors, Ni Cl2 and SKF96365 on [Ca2+]i in distal PVSMC were tested by fluorescence microscope and intracellular [Ca2+] examining system. Results: When PVSMC were perfused with Ca2+-free Krebs solution containing 5 μmol/L nifedipine, 10 μmol/L CPA caused a slight elevation of [Ca2+]i, and acute hypoxia obviously enhanced the [Ca2+]i in PVSMC. When restoration of extracellular [Ca2+] to 2.5 mmol/L, 10 μmol/L CPA caused significant elevation of [Ca2+]i, and acute hypoxia obviously enhanced [Ca2+]i induced by CPA in PVSMC. The SOCC inhibitors, Ni Cl2(500 μmol/L) and SKF96365(50 μmol/L) distinctively attenuated the elevation of [Ca2+]i by hypoxia and CPA. However, NiCl2 and SKF96365 had no effect on high potassium(60 mmol/L KCl Krebs solution) induced elevation of [Ca2+]i in distal PVSMC. Conclusion: Acute hypoxia enhanced the elevation of [Ca2+]i induced by CPA; such effect could be selectively blocked by SOCC inhibitor which indicated that acute hypoxia could enhance the activity of SOCC in rat distal PVSMC.