COMBINED MYOFIBRILLAR AND MITOCHONDRIAL CREATINE-KINASE DEFICIENCY IMPAIRS MOUSE DIAPHRAGM ISOTONIC FUNCTION

Creatine kinase (CK) is an enzyme central to cellular high-energy phos phate 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 o f the diaphragm (Dial from mice with combined myofibrillar and sarcome ric mitochondrial CK deficiency (CK[-/-]) with CK-sufficient controls (Ctl). Maximum velocity of shortening was significantly lower in CK[-/ -] Dia (14.1 +/- 0.9 L-0/s, where L-0 is optimal fiber length) compare d with Ctl Dia (17.5 +/- 1.1 L-0/s) (P < 0.01). Maximum power was obta ined at 0.4-0.5 tetanic force in both groups; absolute maximum power ( 2,293 +/- 138 W/m(2)) and work (201 +/- 9 J/m(2)) were lower in CK[-/- ] Dia compared with Ctl Dia (2,744 +/- 146 W/m(2) and 284 +/- 26 J/m(2 ), respectively) (P < 0.05). The ability of CK[ -/-] Dia to sustain sh ortening 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, co mpared with 61 +/- 5 s in Ctl Dia. We conclude that combined myofibril lar and sarcomeric mitochondrial CK deficiency profoundly impairs Dia power and work. output, underscoring the functional importance of CK d uring dynamic contractions in skeletal muscle.