Myofibrillar or mitochondrial creatine kinase deficiency alone does not impair mouse diaphragm isotonic function

1 Department of Pediatrics, Magee-Womens Research Institute, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania 15213; 2 Department of Cell Biology and Histology, University of Nijmegen, Nijmegen, The Netherlands; and 3 Department of Biological Sciences, Carnegie Mellon University, Pittsburgh, Pennsylvania 15213 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 ~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. respiratory muscle; fatigue; myosin heavy chain