title: Myofibrillar or mitochondrial creatine kinase deficiency alone does not impair mouse diaphragm isotonic function.
abstract: 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.
authors.affiliation: Department of Pediatrics, Magee-Womens Research Institute, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania 15213, USA. jwatchko@mail.magee.edu
authors.forename: J F
authors.initials: JF
authors.lastname: Watchko
authors.forename: M J
authors.initials: MJ
authors.lastname: Daood
authors.forename: B
authors.initials: B
authors.lastname: Wieringa
authors.forename: A P
authors.initials: AP
authors.lastname: Koretsky
mesh_terms: 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
chemical_list: D007527:Isoenzymes; D020033:Protein Isoforms; D003402:Creatine Kinase; D018995:Myosin Heavy Chains