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 expre ssed as 1) cytosolic myofibrillar CK (M-CK) and 2) sarcomeric mitochondrial CK (ScCKmit) isoforms that differ in their subcellular localization. The d iaphragm (Dia) expresses both M-CK and ScCKmit in abundance. We compared th e power and work output of 1) control CK-sufficient (Ctl), 2) M-CK-deficien t [M-CK(-/-)],3) ScCKmit-deficient [ScCKmit(-/-)], and 4) combined M-CK/ScC Kmit-deficient null mutant [CK(-/-)] Dia during repetitive isotonic activat ions to determine the effect of CK phenotype on Dia function. Maximum power was obtained at similar to 0.4 tetanic force in all groups. M-CK(-/-) and ScCKmit(-/-) Dia were able to sustain power and work output at Ctl levels d uring repetitive isotonic activation (75 Hz, 330-ms duration repeated each second at 0.4 tetanic force load), and the duration of sustained Dia shorte ning 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 eith er M-CK or ScCKmit, whereas the complete absence of CK acutely impairs Dia shortening capacity during repetitive activation.