%0 Journal Article
%T Changes in creatine transporter function during cardiac maturation in the rat
%A Alexandra Fischer
%A Michiel ten Hove
%A Liam Sebag-Montefiore
%A Helga Wagner
%A Kieran Clarke
%A Hugh Watkins
%A Craig A Lygate
%A Stefan Neubauer
%J BMC Developmental Biology
%D 2010
%I BioMed Central
%R 10.1186/1471-213x-10-70
%X Rats were studied during the late prenatal period (-2 days before birth) and 7, 13, 21, 33, 50 and 80 days after birth. Activity of cardiac citrate synthase, creatine kinase and its isoenzymes as well as lactate dehydrogenase (LDH) and its isoenzymes demonstrated the well-described shift from anaerobic towards aerobic metabolism. mRNA levels of CrT in the foetal rat hearts, as determined by real-time PCR, were about 30% of the mRNA levels in the adult rat heart and gradually increased during development. Creatine uptake in isolated perfused rat hearts increased significantly from 3.0 nmol/min/gww at 13 days old to 4.9 nmol/min/gww in 80 day old rats. Accordingly, total creatine content in hearts, measured by HPLC, increased steadily during maturation (30 nmol/mg protein (-2 days) vs 87 nmol/mg protein (80 days)), and correlated closely with CrT gene expression.The maturation-dependant alterations of CK and LDH isoenzyme activities and of mitochondrial oxidative capacity were paralleled by a progressive increase of CrT expression, creatine uptake kinetics and creatine content in the heart.Postnatal maturation of the heart is associated with substantial changes in energy metabolism, one of the key determinants of performance. Foetal and newborn hearts are relatively more dependent on anaerobic glycolysis, using mostly glucose, whereas the mature heart is almost exclusively aerobic, with free fatty acids as the predominant substrate [1,2]. The transition from carbohydrate to fatty acid metabolism (i.e. anaerobic to aerobic metabolism) is well documented [3,4] and involves processes, such as maturation of mitochondria and changes in circulating levels of fatty acids and lactate [2]. Thus, the immature myocardium is characterised by lower mitochondrial content [5] and lower activities of both tricarboxylic acid cycle and electron transport chain enzymes [6,7]. Furthermore, contents of both phosphocreatine and total creatine [8], as well as creatine kinase activity [9-11]
%U http://www.biomedcentral.com/1471-213X/10/70