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J Appl Physiol 82: 1416-1423, 1997;
8750-7587/97 $5.00
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Journal of Applied Physiology
Vol. 82, No. 5, pp. 1416-1423, May 1997
EXERCISE AND MUSCLE

Combined myofibrillar and mitochondrial creatine kinase deficiency impairs mouse diaphragm isotonic function

Jon F. Watchko1, Monica J. Daood1, Gary C. Sieck2, John J. Labella1, Bill T. Ameredes3, Alan P. Koretsky4, and Be Wieringa5

1 Department of Pediatrics, Magee-Womens Research Institute, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania 15213; 2 Departments of Anesthesiology, and Physiology and Biophysics, Mayo Clinic and Mayo Medical School, Rochester, Minnesota 55905; 3 Division of Pulmonary, Allergy, and Critical Care Medicine, Department of Medicine, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania 15213; 4 Department of Biological Sciences, Carnegie Mellon University, Pittsburgh, Pennsylvania 15213; and 5 Department of Cell Biology and Histology, University of Nijmegen, Nijmegen, The Netherlands

Received 30 September 1996; accepted in final form 30 December 1996.

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 Lo is 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/m2 and 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.

respiratory muscle; fatigue; myosin heavy chain

0161-7567/97 $5.00 Copyright © 1997 the American Physiological Society




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