Myofibrillar or mitochondrial creatine kinase deficiency alone does not impair mouse diaphragm isotonic function.
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. The diaphragm (Dia) expresses both M-CK and ScCKmit in abundance. We compared the power and work output of 1) control CK-sufficient (Ctl), 2) M-CK-deficient [M-CK(-/-)], 3) ScCKmit-deficient [ScCKmit(-/-)], and 4) combined M-CK/ScCKmit-deficient null mutant [CK(-/-)] Dia during repetitive isotonic activations to determine the effect of CK phenotype on Dia function. Maximum power was obtained at approximately 0.4 tetanic force in all groups. M-CK(-/-) and ScCKmit(-/-) Dia were able to sustain power and work output at Ctl levels during repetitive isotonic activation (75 Hz, 330-ms duration repeated each second at 0.4 tetanic force load), and the duration of sustained Dia shortening was 67 +/- 4 s in M-CK(-/-), 60 +/- 4 s in ScCKmit(-/-), and 62 +/- 5 s in Ctl Dia. In contrast, CK(-/-) Dia power and work declined acutely and failed to sustain shortening altogether by 40 +/- 6 s. We conclude that Dia power and work output are not absolutely dependent on the presence of either M-CK or ScCKmit, whereas the complete absence of CK acutely impairs Dia shortening capacity during repetitive activation.
Watchko
J F
JF
Department of Pediatrics, Magee-Womens Research Institute, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania 15213, USA. jwatchko@mail.magee.edu
Daood
M J
MJ
Wieringa
B
B
Koretsky
A P
AP
D000818:Animals; D003402:Creatine Kinase / Q000172:deficiency* / Q000235:genetics; D003964:Diaphragm / Q000201:enzymology* / Q000502:physiology*; D066298:In Vitro Techniques; D007527:Isoenzymes; D007551:Isotonic Contraction / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008931:Mitochondria, Muscle / Q000201:enzymology*; D009210:Myofibrils / Q000201:enzymology*; D018995:Myosin Heavy Chains / Q000378:metabolism; D010641:Phenotype; D020033:Protein Isoforms / Q000378:metabolism
D007527:Isoenzymes; D020033:Protein Isoforms; D003402:Creatine Kinase; D018995:Myosin Heavy Chains