Antisense inhibition of Na+/Ca2+ exchange during anoxia/reoxygenation in ventricular myocytes.
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.
Eigel
B N
BN
Department of Molecular and Biomedical Pharmacology, University of Kentucky College of Medicine, Lexington, Kentucky 40536-0298, USA. bneige0@pop.uky.edu
Hadley
R W
RW
D000818:Animals; D002118:Calcium / Q000378:metabolism; D015687:Cell Hypoxia / Q000502:physiology; D002478:Cells, Cultured; D005260:Female; D006168:Guinea Pigs; D018485:Muscle Fibers, Skeletal / Q000166:cytology / Q000378:metabolism*; D017202:Myocardial Ischemia / Q000378:metabolism; D015428:Myocardial Reperfusion Injury / Q000378:metabolism*; D009206:Myocardium / Q000166:cytology / Q000378:metabolism*; D016376:Oligonucleotides, Antisense / Q000494:pharmacology; D019831:Sodium-Calcium Exchanger / Q000235:genetics* / Q000378:metabolism
D016376:Oligonucleotides, Antisense; D019831:Sodium-Calcium Exchanger; D002118:Calcium