Antisense inhibition of Na+/Ca2+ exchange during anoxia/reoxygenation in ventricular myocytes

被引:40
作者
Eigel, BN [1 ]
Hadley, RW [1 ]
机构
[1] Univ Kentucky, Coll Med, Dept Mol & Biomed Pharmacol, Lexington, KY 40536 USA
来源
AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY | 2001年 / 281卷 / 05期
关键词
hypoxia; calcium; heart; ischemia; sodium/calcium exchanger;
D O I
10.1152/ajpheart.2001.281.5.H2184
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
This study investigated the role of the Na+/Ca2+ exchanger (NCX) in regulating cytosolic intracellular Ca2+ concentration ([Ca2+](i)) during anoxia/reoxygenation in guinea pig ventricular myocytes. The hypothesis that the NCX is the predominant mechanism mediating [Ca2+](i) overload in this model was tested through inhibition of NCX expression by an antisense oligonucleotide. Immunocytochemistry revealed that this antisense oligonucleotide, directed at the area around the start site of the guinea pig NCX1, specifically reduced NCX expression in cultured adult myocytes by 90 +/-4%. Antisense treatment inhibited evoked NCX activity by 94 +/-3% and decreased the rise in [Ca2+](i) during anoxia/reoxygenation by 95 +/-3%. These data suggest that NCX is the predominant mechanism mediating Ca2+ overload during anoxia/reoxygenation in guinea-pig ventricular myocytes.
引用
收藏
页码:H2184 / H2190
页数:7
相关论文
共 47 条
[1]  
ALTSCHULD RA, 1985, BASIC RES CARDIOL, V80, P151
[2]   NA-H EXCHANGE IN MYOCARDIUM - EFFECTS OF HYPOXIA AND ACIDIFICATION ON NA AND CA [J].
ANDERSON, SE ;
MURPHY, E ;
STEENBERGEN, C ;
LONDON, RE ;
CALA, PM .
AMERICAN JOURNAL OF PHYSIOLOGY, 1990, 259 (06) :C940-C948
[3]   Stimulation of the Na+/Ca2+ exchanger by phenylephrine, angiotensin II and endothelin I [J].
Ballard, C ;
Schaffer, S .
JOURNAL OF MOLECULAR AND CELLULAR CARDIOLOGY, 1996, 28 (01) :11-17
[4]   Myocardial segment shrinkage during coronary reperfusion in situ - Relation to hypercontracture and myocardial necrosis [J].
Barrabes, JA ;
GarciaDorado, D ;
RuizMeana, M ;
Piper, HM ;
Solares, J ;
Gonzalez, MA ;
Oliveras, J ;
Herrejon, MP ;
Soler, JS .
PFLUGERS ARCHIV-EUROPEAN JOURNAL OF PHYSIOLOGY, 1996, 431 (04) :519-526
[5]   ATP stimulation of Na+/Ca2+ exchange in cardiac sarcolemmal vesicles [J].
Berberián, G ;
Hidalgo, C ;
DiPolo, R ;
Beaugé, L .
AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY, 1998, 274 (03) :C724-C733
[6]   ATP-DEPENDENT REGULATION OF SODIUM-CALCIUM EXCHANGE IN CHINESE-HAMSTER OVARY CELLS TRANSFECTED WITH THE BOVINE CARDIAC SODIUM-CALCIUM EXCHANGER [J].
CONDRESCU, M ;
GARDNER, JP ;
CHERNAYA, G ;
ACETO, JF ;
KROUPIS, C ;
REEVES, JP .
JOURNAL OF BIOLOGICAL CHEMISTRY, 1995, 270 (16) :9137-9146
[7]   Overexpression of the cardiac Na+/Ca2+ exchanger increases susceptibility to ischemia/reperfusion injury in male, but not female, transgenic mice [J].
Cross, HR ;
Lu, LY ;
Steenbergen, C ;
Philipson, KD ;
Murphy, E .
CIRCULATION RESEARCH, 1998, 83 (12) :1215-1223
[8]   Intramitochondrial [Ca2+] and membrane potential in ventricular myocytes exposed to anoxia-reoxygenation [J].
Delcamp, TJ ;
Dales, C ;
Ralenkotter, L ;
Cole, PS ;
Hadley, RW .
AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY, 1998, 275 (02) :H484-H494
[9]  
DOERING AE, 1993, J PHYSIOL-LONDON, V466, P481
[10]  
Eigel BN, 2000, CIRCULATION, V102, P136