Combined deficiency op myofibrillah and mitochondrial creatine kimask in diaphragm impairs power output during repetitive isotonic contractions

Creatine kinase (CK) has been implicated in the maintenance of skeletal muscle intracellular energy supply via its ATP buffering capacity. The localization of CK at the mitochondria (CK-mi) and myofibril (CK-M) is postulated to increase the efficiency of energy transduction allowing increased muscle performance. We compared the in vitro (37°) force-velocity properties of the diaphragm (DIA) from I) transgenic mice deficient in both CK-M and CK-mi (double null mutant) and 2} wild type controls (CTL) to characterize the role of CK. Optimal muscle length (L_o: 7.8±0.4 mm) and peak force at L0 (P_o: 22±1 N/cm²) were not different between CTL and double null mutant DIA. Maximum velocity of shortening was lower in CKM/CK-mi deficient DIA (V_max: 14±2 Lo/s) vs. CTL DIA (V_max: 17±2 Lo/s) ; peak power output was obtained at 0.4 P_o in both groups. The ability of CK-M/CK-mi deficient DIA to sustain shortening during repetitive isotonic contractions (75 Hz, 330 me duration repeated each sec at 0.4 P_o load) was markedly impaired. CK-M/CK-mi deficient DIA velocity of shortening and power declined to zero by 27±4 sec, whereas CTL DIA power was sustained at 65% of baseline. We conclude that combined CK-M/CK-mi deficiency in DIA profoundly alters shortening capacity during repetitive ieotonic activation, underscoring the functional importance of CK in skeletal muscle.