Muscle creatine kinase-deficient mice. II. Cardiac and skeletal muscles exhibit tissue-specific adaptation of the mitochondrial function.
Functional properties of in situ mitochondria and of mitochondrial creatine kinase were studied in saponin-skinned fibers taken from normal and M-creatine kinase-deficient mice. In control animals, apparent Km values of mitochondrial respiration for ADP in cardiac (ventricular) and slow-twitch (soleus) muscles (137 +/- 16 microM and 209 +/- 10 microM, respectively) were manyfold higher than that in fast-twitch (gastrocnemius) muscle (7.5 +/- 0.5 microM). Creatine substantially decreased the Km values only in cardiac and slow-twitch muscles (73 +/- 11 microM and 131 +/- 21 microM, respectively). As compared to control, in situ mitochondria in transgenic ventricular and slow-twitch muscles showed two times lower Km values for ADP, and the presence of creatine only slightly decreased the Km values. In mutant fast-twitch muscle, a decrease rather than increase in mitochondrial sensitivity to ADP occurred, but creatine still had no effect. Furthermore, in these muscles, relatively low oxidative capacity was considerably elevated. It is suggested that in the mutant mice, impairment of energy transport function in ventricular and slow-twitch muscles is compensated by a facilitation of adenine nucleotide transportation between mitochondria and cellular ATPases; in fast-twitch muscle, mainly energy buffering function is depressed, and that is overcome by an increase in energy-producing potential.
Veksler
V I
VI
Laboratoire de Cardiologie Cellulaire et Moléculaire, CJF INSERM 92-11, Faculté de Pharmacie, Université Paris-Sud, Châtenay-Malabry, France.
Kuznetsov
A V
AV
Anflous
K
K
Mateo
P
P
van Deursen
J
J
Wieringa
B
B
Ventura-Clapier
R
R
D000222:Adaptation, Physiological; D000244:Adenosine Diphosphate / Q000494:pharmacology; D000263:Adenylate Kinase / Q000378:metabolism; D000818:Animals; D003402:Creatine Kinase / Q000172:deficiency* / Q000235:genetics; D005260:Female; D066298:In Vitro Techniques; D007527:Isoenzymes; D007700:Kinetics; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D008929:Mitochondria, Heart / Q000187:drug effects / Q000201:enzymology; D008931:Mitochondria, Muscle / Q000187:drug effects / Q000201:enzymology; D008954:Models, Biological; D018656:Muscle Fibers, Fast-Twitch / Q000201:enzymology; D018657:Muscle Fibers, Slow-Twitch / Q000201:enzymology; D018482:Muscle, Skeletal / Q000201:enzymology*; D009206:Myocardium / Q000201:enzymology*; D010101:Oxygen Consumption; D014018:Tissue Distribution
D007527:Isoenzymes; D000244:Adenosine Diphosphate; D003402:Creatine Kinase; D000263:Adenylate Kinase