Absence of myofibrillar creatine kinase and diaphragm isometric function during repetitive activation.
Creatine kinase (CK) provides ATP buffering in skeletal muscle and is expressed as 1) cytosolic myofibrillar CK (M-CK) and 2) sarcomeric mitochondrial CK (ScCKmit) isoforms that differ in their subcellular localization. We compared the isometric contractile and fatigue properties of 1) control CK-sufficient (Ctl), 2) M-CK-deficient (M-CK[-/-]), and 3) combined M-CK/ScCKmit-deficient null mutant (CK[-/-]) diaphragm (Dia) to determine the effect of the absence of M-CK activity on Dia performance in vitro. Baseline contractile properties were comparable across groups except for specific force, which was approximately 16% lower in CK[-/-] Dia compared with M-CK[-/-] and Ctl Dia. During repetitive activation (40 Hz, (1)/(3) duty cycle), force declined in all three groups. This decline was significantly greater in CK[-/-] Dia compared with Ctl and M-CK[-/-] Dia. The pattern of force decline did not differ between M-CK[-/-] and Ctl Dia. We conclude that Dia isometric muscle function is not absolutely dependent on the presence of M-CK, whereas the complete absence of CK acutely impairs isometric force generation during repetitive activation.
LaBella
J J
JJ
Department of Pediatrics, Magee-Womens Research Institute, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania 15213, USA.
Daood
M J
MJ
Koretsky
A P
AP
Roman
B B
BB
Sieck
G C
GC
Wieringa
B
B
Watchko
J F
JF
D000263:Adenylate Kinase / Q000378:metabolism; D000818:Animals; D003402:Creatine Kinase / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D003600:Cytosol / Q000378:metabolism; D003964:Diaphragm / Q000166:cytology / Q000201:enzymology* / Q000502:physiology*; D004586:Electrophoresis; D004789:Enzyme Activation; D006003:Glycogen / Q000378:metabolism; D066298:In Vitro Techniques; D007527:Isoenzymes; D007537:Isometric Contraction / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D008931:Mitochondria, Muscle / Q000201:enzymology / Q000378:metabolism; D009210:Myofibrils / Q000201:enzymology*; D010641:Phenotype; D013385:Succinate Dehydrogenase / Q000378:metabolism
D007527:Isoenzymes; D006003:Glycogen; D013385:Succinate Dehydrogenase; D003402:Creatine Kinase; D000263:Adenylate Kinase