Hypoxia‐induced cytosolic calcium influx is mediated primarily by the reverse mode of Na+/Ca2+ exchanger in smooth muscle cells of fetal small pulmonary arteries. Issue 6 (June 2014)

• Record Type: Journal Article
• Authors: Sun, Yanjuan; Ye, Lincai; Liu, Jinfen; Hong, Haifa
• Is Part Of: Journal of obstetrics and gynaecology research. Volume 40:Issue 6(2014:Jun.)
• Page Start: 1578
• Page End: 1583
• Publication Date: 2014-06
• Subjects: Gynecology -- Periodicals; Obstetrics -- Periodicals; 618.1005
• DOI: 10.1111/jog.12391
• Languages: English
• ISSNs: 1341-8076

Abstract

<abstract abstract-type="main"> <title>Abstract</title> <sec id="jog12391-sec-0001" sec-type="section"> <title>Aim</title> <p>Constriction of small pulmonary arteries and high resistance of pulmonary circulation are important for maintaining fetal circulation before birth. In this study, we investigated how cytosolic free calcium concentration ([Ca<sup>2+</sup>]<sub>i</sub>) in fetal lamb small pulmonary artery smooth muscle cells (SPASMC) was affected by hypoxia and regulated by calcium pumps during this process.</p> </sec> <sec id="jog12391-sec-0002" sec-type="section"> <title>Methods</title> <p>(Ca<sup>2+</sup>)<sub>i</sub> in response to acute hypoxia was determined spectrofluorometrically with fluo‐3AM in cultured fetal SPASMC. Chemicals or solutions, including ryanodine, 2‐aminoethoxydiphenyl borate, Ca<sup>2+</sup>‐free solution with 20 mmol ethyleneglycoltetraacetic (EGTA), nimodipine, Na<sup>+</sup>‐free medium and KB‐R7943, were administrated at the same time point when samples were exposed to acute hypoxia.</p> </sec> <sec id="jog12391-sec-0003" sec-type="section"> <title>Results</title> <p>(Ca<sup>2+</sup>)<sub>i</sub> in fetal lamb SPASMC increased under acute hypoxia. 2‐Aminoethoxydiphenyl borate, an inhibitor of inositol triphosphate calcium store, partially attenuated the (Ca<sup>2+</sup>)<sub>i</sub> increase after 6‐min treatment. Ryanodine, an inhibitor of ryanodine‐sensitive calcium stores, had no effect on the (Ca<sup>2+</sup>)<sub>i</sub> increase. Ca<sup>2+</sup>‐free solution with EGTA completely abolished this increase. Both nimodipine, that blocks the voltage‐gated calcium channel, and KB‐R7943, that inhibits the reverse mode of Na<sup>+</sup>/Ca<sup>2+</sup> exchanger, greatly diminished the hypoxia‐induced (Ca<sup>2+</sup>)<sub>i</sub> increase. The inhibitory effect of KB‐R7943 was stronger than nimodipine, evidenced by the fact that (Ca<sup>2+</sup>)<sub>i</sub> dropped near to the baseline level in the presence of KB‐R7943 at a later time point. Low extracellular Na<sup>+</sup> concentration enhanced the hypoxia‐induced increase of (Ca<sup>2+</sup>)<sub>i</sub>.</p> </sec> <sec id="jog12391-sec-0004" sec-type="section"> <title>Conclusion</title> <p>These results suggest that hypoxia‐induced Ca<sup>2+</sup> increase in fetal SPASMC results from cytosolic Ca<sup>2+</sup> influx mediated primarily by the reverse mode of Na<sup>+</sup>/Ca<sup>2+</sup> exchanger.</p> </sec> </abstract>