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(Circulation. 1996;93:310-317.)
© 1996 American Heart Association, Inc.

Articles

Coupling Between Myosin ATPase Cycle and Creatine Kinase Cycle Facilitates Cardiac Actomyosin Sliding In Vitro

A Clue to Mechanical Dysfunction During Myocardial Ischemia

Masataka Sata, MD; Seiryo Sugiura, MD; Hiroshi Yamashita, MD; Shin-ichi Momomura, MD; Takashi Serizawa, MD

From the Second Department of Internal Medicine, Faculty of Medicine, University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113, Japan.

Correspondence to Masataka Sata, MD, Department of Physiology, University of Massachusetts Medical Center, 55 Lake Ave N, Worcester, MA 01655-0127. E-mail mxs125@po.cwru.edu.

Background There is much evidence to support the favorable effects of the phosphocreatine shuttle on myocardial contraction and relaxation. However, experiments in which cardiac muscle fiber or myofibril was used have not elucidated its precise mechanism.

Methods and Results Active movements of fluorescently labeled actin filaments on a cardiac myosin layer coimmobilized with creatine kinase (CK) onto a nitrocellulose-coated glass coverslip were studied under various concentrations of adenine nucleotides. At a constant phosphocreatine concentration (5 mmol/L, pH 7.1), the relation of sliding velocity to MgATP concentration followed Michaelis-Menten kinetics. The apparent K_m was significantly smaller in the presence of CK (0.041±0.001 mmol/L) than in the absence of CK (0.080±0.001 mmol/L), indicating that coattached CK facilitated the propelling of actin filaments by the myosin ATPase. This phenomenon was also seen under acidic conditions (pH 6.7) as well as in the presence of inorganic phosphate (10 mmol/L). At a constant MgATP concentration (1 mmol/L), the inhibitory effect of MgADP on the actin-myosin interaction was weaker in the presence of CK than in the absence of CK. Another ATP-regenerating system, pyruvate kinase and phospho(enol)pyruvate, while maintaining a low ratio of [MgADP] to [MgATP], did not reduce the K_m value (0.156±0.001 mmol/L), suggesting that the effect of coattached CK was not achieved only by prevention of MgADP accumulation.

Conclusions Coupling between the ATPase cycle and the CK cycle may serve not only to maintain the ATP concentration within the myofibril but also to provide optimal conditions for cardiac actomyosin interaction. Consideration of this coupling will offer a clue to elucidating the systolic or diastolic dysfunction during myocardial ischemia or reperfusion.

Key Words: creatine kinase • mechanics • ischemia

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