CaATP prolongs strong actomyosin binding and promotes futile myosin stroke
Calcium plays an essential role in muscle contraction, regulating actomyosin interaction by binding troponin of thin filaments. There are several buffers for calcium in muscle, and those buffers play a crucial role in the formation of the transient calcium wave in sarcomere upon muscle activation. One such calcium buffer in muscle is ATP. ATP is a fuel molecule, and the important role of MgATP in muscle is to bind myosin and supply energy for the power stroke. Myosin is not a specific ATPase, and CaATP also supports myosin ATPase activity. The concentration of CaATP in sarcomeres reaches 1% of all ATP available. Since 294 myosin molecules form a thick filament, naïve estimation gives three heads per filament with CaATP bound, instead of MgATP. We found that CaATP dissociates actomyosin slower than MgATP, thus increasing the time of the strong actomyosin binding. The rate of the basal CaATPase is faster than that of MgATPase, myosin readily produces futile stroke with CaATP. When calcium is upregulated, as in malignant hyperthermia, kinetics of myosin and actomyosin interaction with CaATP suggest that myosin CaATPase activity may contribute to observed muscle rigidity and enhanced muscle thermogenesis.
KeywordsMyosin Muscle ATP Calcium Malignant hyperthermia Transient kinetics
This work was supported by National Institutes of Health (Grant No. HL132315) and by funds provided by the University of North Carolina at Charlotte.
Compliance with ethical standards
Conflict of interest
The authors declare that they have no conflicts of interest with the contents of this article.
Myosin and actin were produced from rabbit skeletal tissue. All experimental protocols were approved by the Institutional Animal Care and Use Committee of UNC Charlotte and all experiments were performed in accordance with relevant guidelines and regulations.
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