Postnatal maturation of the heart is characterized by decreasing tolerance to ischemia/reperfusion (I/R) injury associated with significant changes in mitochondrial function. The aim of this study is to test the hypothesis that the role of the mitochondrial membrane permeability transition pore (MPTP) in the I/R injury differs in the neonatal and in the adult heart. For this purpose, the effect of blockade of MPTP on the degree of I/R injury and the sensitivity of MPTP to swelling-inducing agents was compared in hearts from neonatal (7 days old) and adult (90 days old) Wistar rats. It was found that the release of NAD(+) from the perfused heart induced by I/R can be prevented by sanglifehrin A (SfA) only in the adult myocardium; SfA had no protective effect in the neonatal heart. Furthermore, the extent of Ca-induced swelling of mitochondria from neonatal rats was significantly lower than that from the adult animals; mitochondria from neonatal rats were more resistant at higher concentrations of calcium. In addition, not only the extent but also the rate of calcium-induced swelling was about twice higher in adult than in neonatal mitochondria. The results support the idea that lower sensitivity of the neonatal MPTP to opening may be involved in the mechanism of the higher tolerance of the neonatal heart to I/R injury.

Centre for Cardiovascular Research Institute of Physiology Academy of Sciences of the Czech Republic Vídenská 1083 14220 Prague 4 Czech Republic

Zobrazit více v PubMed

Nature. 2005 Mar 31;434(7033):652-8 PubMed

Nature. 1966 Aug 6;211(5049):646-7 PubMed

Nature. 2005 Mar 31;434(7033):658-62 PubMed

Biochim Biophys Acta. 1961 Feb 18;47:411-2 PubMed

Biochem Soc Trans. 2006 Apr;34(Pt 2):232-7 PubMed

Circ Res. 1979 Feb;44(2):263-79 PubMed

J Mol Cell Cardiol. 1998 Apr;30(4):857-65 PubMed

Physiol Res. 2004;53(1):119-22 PubMed

Am J Physiol Cell Physiol. 2007 Feb;292(2):C708-18 PubMed

Cardiovasc Res. 2006 May 1;70(2):191-9 PubMed

Physiol Rev. 1999 Jul;79(3):635-59 PubMed

Cardiovasc Res. 2004 Feb 15;61(3):372-85 PubMed

Eur J Biochem. 1995 May 15;230(1):235-41 PubMed

J Mol Cell Cardiol. 2003 Mar;35(3):321-30 PubMed

J Biol Chem. 2001 Jan 26;276(4):2571-5 PubMed

Physiol Res. 2001;50(3):237-45 PubMed

Mol Cell Biochem. 1998 Jul;184(1-2):379-91 PubMed

J Biol Chem. 2002 Sep 20;277(38):34793-9 PubMed

Pediatr Res. 2002 Oct;52(4):561-7 PubMed

J Physiol. 2000 Nov 15;529 Pt 1:37-47 PubMed

J Mol Cell Cardiol. 1993 Dec;25(12):1461-9 PubMed

Circ Res. 1980 Apr;46(4):503-12 PubMed

Am J Physiol. 1991 Jul;261(1 Pt 2):H1-8 PubMed

Z Anat Entwicklungsgesch. 1971;133(3):288-304 PubMed

Arch Biochem Biophys. 1976 Aug;175(2):627-34 PubMed

Can J Physiol Pharmacol. 1995 Jan;73(1):50-4 PubMed

J Mol Cell Cardiol. 1993 Jun;25(6):733-40 PubMed

Physiol Res. 2008;57(5):793-796 PubMed

FEBS J. 2006 May;273(10):2077-99 PubMed

J Mol Cell Cardiol. 1995 Aug;27(8):1689-701 PubMed

Eur J Biochem. 1996 Nov 1;241(3):895-900 PubMed

J Bioenerg Biomembr. 1995 Dec;27(6):583-96 PubMed

J Mol Cell Cardiol. 1995 Aug;27(8):1731-43 PubMed

Anal Biochem. 1973 Jun;53(2):452-8 PubMed

J Physiol. 1975 Aug;249(3):469-95 PubMed

Presse Med. 1998 Dec 12;27(39):2100-4 PubMed

J Biol Chem. 1951 Nov;193(1):265-75 PubMed

Sex Differences in Cardiac Tolerance to Oxygen Deprivation - 40 Years of Cardiovascular Research

Nitric oxide is involved in the cardioprotection of neonatal rat hearts, but not in neonatal ischemic postconditioning

Sixty Years of Heart Research in the Institute of Physiology of the Czech Academy of Sciences

The Mitochondrial Permeability Transition Pore-Current Knowledge of Its Structure, Function, and Regulation, and Optimized Methods for Evaluating Its Functional State

Possible role of mitochondrial K-ATP channel and nitric oxide in protection of the neonatal rat heart

Sex difference in the sensitivity of cardiac mitochondrial permeability transition pore to calcium load

Characterization of calcium, phosphate and peroxide interactions in activation of mitochondrial swelling using derivative of the swelling curves