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Analysis of Cardiac Contractile Dysfunction and Ca2+ Transients in Rodent Myocytes
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Changes in creatine transporter function during cardiac maturation in the rat.

Alexandra Fischer1, Michiel Ten Hove, Liam Sebag-Montefiore

  • 1Department of Cardiovascular Medicine, Wellcome Trust Centre for Human Genetics, University of Oxford, Roosevelt Drive, Oxford, UK.

BMC Developmental Biology
|June 24, 2010
PubMed
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The creatine transporter (CrT) in rat hearts increases with age, enhancing creatine uptake and levels. This developmental regulation supports the shift towards aerobic metabolism in the maturing heart.

Area of Science:

  • Cardiovascular Physiology
  • Developmental Biology
  • Biochemistry

Background:

  • Immature heart muscle relies on non-oxidative energy pathways, showing lower creatine kinase (CK) shuttle capacity.
  • Myocardial energy transfer increases with maturation, but the underlying mechanisms are not fully understood.
  • Heart creatine is exclusively taken up via the creatine transporter protein (CrT), which is not synthesized in the heart.

Purpose of the Study:

  • To investigate the ontogenic regulation of the creatine transporter (CrT) in the developing rat heart.
  • To examine the relationship between CrT gene expression, creatine uptake, and myocardial creatine levels during maturation.

Main Methods:

  • Real-time PCR to quantify CrT mRNA levels in rat hearts from prenatal to adult stages.

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  • Isolated perfused rat hearts to measure creatine uptake kinetics at various developmental time points.
  • High-performance liquid chromatography (HPLC) to determine total creatine content in myocardial tissue.

    • Main Results:

    • CrT mRNA levels in fetal rat hearts were 30% of adult levels, increasing progressively with age.
    • Cardiac creatine uptake significantly increased from 3.0 nmol/min/gww at 13 days to 4.9 nmol/min/gww at 80 days.
    • Total myocardial creatine content rose steadily from 30 nmol/mg protein in fetuses to 87 nmol/mg protein in 80-day-old rats, correlating with CrT expression.

    Conclusions:

    • Maturation of the heart involves increased creatine transporter (CrT) expression and function.
    • Enhanced CrT activity leads to higher myocardial creatine levels during development.
    • These changes support the shift from anaerobic to aerobic metabolism in the maturing heart.