Absence of myofibrillar creatine kinase and diaphragm isometric function during repetitive activation

1 Department of Pediatrics, Magee-Womens Research Institute, University of Pittsburgh School of Medicine, Pittsburgh 15213; 2 Department of Biological Sciences, Carnegie Mellon University, Pittsburgh, Pennsylvania 15213; 3 Departments of Anesthesiology, and Physiology and Biophysics, Mayo Clinic and Mayo Medical School, Rochester, Minnesota 55905; and 4 Department of Cell Biology and Histology, University of Nijmegen, Nijmegen, The Netherlands 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 ~16% lower in CK[ / ] Dia compared with M-CK[ / ] and Ctl Dia. During repetitive activation (40 Hz, 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. respiratory muscle; fatigue; oxidative capacity