Compartmentation of creatine kinases during perinatal development of mammalian heart.
Maturation of the cardiac cell is characterized by increasing diversity of isozymic expression of creatine kinases. Expression of the M-CK isozyme always precedes that of mitochondrial isozyme (mi-CK), however the expression of an isoform does not inform about its localization or cellular function. The functional role of isozymes binding to sites of energy utilization and production characteristic of the adult myocardium can be evidenced by the functional coupling of M-CK to myofibrillar ATPase and mito-CK to translocase in Triton X-100 and saponin skinned fibers. Functional activity of M-CK and mito-CK were investigated during perinatal development. Both functional activities appear during late fetal life in species mature at birth like guinea pig, and in the first postnatal weeks in immature species like rat or rabbit. Thus, the functional activity of bound CK isozymes is not associated with birth per se but with the general process of cell maturation. Localization of CK in the cytosol appears optimal for the transfer of glycolytic production of ATP to sites of utilization in an immature heart. During cell maturation, the increasing contribution of oxidative phosphorylation to ATP production, the apparition and binding of mi-CK to mitochondria, the binding of M-CK to myofibrils, turn the cell in a compartmentalized system of energy production. This provides the cellular basis for energy transfer by the PCr-Cr-CK system between sites of ATP production and utilization. Compartmentation of both Ca handling and energy turnover leads to a highly structured cell organization and could be essential for the efficiency of heart function.
Hoerter
J A
JA
CJF INSERM 92-11, Université Paris-Sud, Faculté de Pharmacie, Chatenay Malabry, France.
Ventura-Clapier
R
R
Kuznetsov
A
A
D000818:Animals; D000831:Animals, Newborn; D003402:Creatine Kinase / Q000378:metabolism*; D005314:Embryonic and Fetal Development; D005318:Fetal Heart / Q000201:enzymology*; D006168:Guinea Pigs; D006321:Heart / Q000254:growth & development; D007527:Isoenzymes; D008929:Mitochondria, Heart / Q000201:enzymology; D009206:Myocardium / Q000166:cytology / Q000201:enzymology*; D009210:Myofibrils / Q000201:enzymology; D011817:Rabbits; D051381:Rats
D007527:Isoenzymes; D003402:Creatine Kinase