From energy store to energy flux: a study in creatine kinase-deficient fast skeletal muscle.
Fast-twitch skeletal muscle of mice deficient in cytosolic and mitochondrial creatine kinase isoforms (CK-/-) lack burst activity but can sustain prolonged contractile activity, suggesting that adaptive mechanisms can regulate local adenine nucleotide turnover. We investigated whether direct energy and signal channeling between mitochondria and sarcoplasmic reticulum (SR) or myofilaments may exist that compensate for the lack of CK isoenzymes. Oxidative capacity of fast-twitch muscle was increased twofold in CK-/- mice. Energy cross talk between organelles was studied in muscle fibers with permeabilized sarcolemma. Energy supply to SR was estimated by analyzing the tension transient induced by caffeine and energy supply to myofilaments was estimated by the relaxation of rigor tension, both under different conditions of energy supply. In normal mice, ATP directly produced by mitochondria was not able to sustain calcium uptake and to relax rigor tension as efficiently as ATP produced by bound CK. However, in CK-/- mice, mitochondria ability to provide ATP for calcium uptake and relaxation of rigor tension was dramatically enhanced, suggesting a direct ATP/ADP channeling between sites of energy production mitochondria) and energy utilization in CK-/- mice. These results demonstrate two possible patterns of energy transport in muscle cells: energy store with phosphocreatine and energy flux through mitochondria.
Kaasik
Allen
A
U-446 INSERM, Université Paris-Sud, 92296 Châtenay-Malabry, France.
Veksler
Vladimir
V
Boehm
Ernest
E
Novotova
Marta
M
Ventura-Clapier
Renée
R
D000255:Adenosine Triphosphate / Q000378:metabolism* / Q000494:pharmacology; D000818:Animals; D002110:Caffeine / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism; D003402:Creatine Kinase / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D008931:Mitochondria, Muscle / Q000187:drug effects / Q000378:metabolism; D018656:Muscle Fibers, Fast-Twitch / Q000378:metabolism*; D018482:Muscle, Skeletal / Q000378:metabolism*; D012519:Sarcoplasmic Reticulum / Q000187:drug effects / Q000378:metabolism
D002110:Caffeine; D000255:Adenosine Triphosphate; D003402:Creatine Kinase; D002118:Calcium