Ameredes, Bill T.

We hypothesized that decrements in maximum power output (W˙max) of the rat diaphragm (Dia) muscle with repetitive activation are due to a disproportionate reduction in force (force fatigue) compared with a slowing of shortening velocity (velocity fatigue). Segments of midcostal Dia muscle were mounted in vitro (26°C) and stimulated directly at 75 Hz in 400-ms-duration trains repeated each second (duty cycle = 0.4) for 120 s. A novel technique was used to monitor instantaneous reductions in maximum specific force (Po) andW˙maxduring fatigue. During each stimulus train, activation was isometric for the initial 360 ms during which Powas measured; the muscle was then allowed to shorten at a constant velocity (30% Vmax) for the final 40 ms, and W˙maxwas determined. Compared with initial values, after 120 s of repetitive activation, PoandW˙maxdecreased by 75 and 73%, respectively. Maximum shortening velocity was measured in two ways: by extrapolation of the force-velocity relationship ( Vmax) and using the slack test [maximum unloaded shortening velocity ( Vo)]. After 120 s of repetitive activation, Vmaxslowed by 44%, whereas Voslowed by 22%. Thus the decrease inW˙maxwith repetitive activation was dominated by force fatigue, with velocity fatigue playing a secondary role. On the basis of a greater slowing of Vmaxvs. Vo, we also conclude that force and power fatigue cannot be attributed simply to the total inactivation of the most fatigable fiber types.

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.