Labella, John J.

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, [Formula: see text] 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.

Watchko, Jon F., Monica J. Daood, Gary C. Sieck, John J. LaBella, Bill T. Ameredes, Alan P. Koretsky, and Be Wieringa. Combined myofibrillar and mitochondrial creatine kinase deficiency impairs mouse diaphragm isotonic function. J. Appl. Physiol. 82(5): 1416–1423, 1997.—Creatine kinase (CK) is an enzyme central to cellular high-energy phosphate metabolism in muscle. To characterize the physiological role of CK in respiratory muscle during dynamic contractions, we compared the force-velocity relationships, power, and work output characteristics of the diaphragm (Dia) from mice with combined myofibrillar and sarcomeric mitochondrial CK deficiency (CK[−/−]) with CK-sufficient controls (Ctl). Maximum velocity of shortening was significantly lower in CK[−/−] Dia (14.1 ± 0.9 Lo/s, where Lois optimal fiber length) compared with Ctl Dia (17.5 ± 1.1 Lo/s) ( P < 0.01). Maximum power was obtained at 0.4–0.5 tetanic force in both groups; absolute maximum power (2,293 ± 138 W/m2) and work (201 ± 9 J/m2) were lower in CK[−/−] Dia compared with Ctl Dia (2,744 ± 146 W/m2and 284 ± 26 J/m2, respectively) ( P < 0.05). The ability of CK[−/−] Dia to sustain shortening during repetitive isotonic activation (75 Hz, 330-ms duration repeated each second at 0.4 tetanic force load) was markedly impaired, with CK[−/−] Dia power and work declining to zero by 37 ± 4 s, compared with 61 ± 5 s in Ctl Dia. We conclude that combined myofibrillar and sarcomeric mitochondrial CK deficiency profoundly impairs Dia power and work output, underscoring the functional importance of CK during dynamic contractions in skeletal muscle.