Masticatory myosin (MHC-M) is an ancient isoform found in jaw closing muscles of gray squirrels ( Sciurus carolinensis ) but not in rats ( Rattus norvegicus ). Force-velocity (F-V) measurements on whole muscle, performed using an afterload protocol, show that squirrel muscle is as fast as rat muscle. Surprisingly, in vitro motility (IVM) measurements show that MHC-M isolated from squirrel muscle is slower (V∼800 nm/s) than fast myosins from rat muscle (V∼4000 nm/s). To understand this discrepancy, we developed a mathematical model of IVM to determine the kinetic scheme and rate constants that best explain our measurements. We find that MHC-M is slow (attachment rate, k a =6 s −1 , ADP release rate, k D = 60 s −1 , ATP-binding rate, k T = 1 μM −1 s −1 ) compared to fast rat myosins (k a = 22 s −1 , k D = 460 s −1 , k T = 2.6 μM −1 s −1 ). These kinetics, when added to a muscle model where cross-bridges interact with parallel and series elastic elements, can reproduce our muscle measurements, including the comparable velocities of squirrel and rat muscle. These results arise because of a transient that occurs at the onset of muscle activation. For rat muscle, this transient produces velocities similar to IVM velocity; for squirrel muscle, it yields velocities 4–5 times higher. The model makes two testable predictions. First, predicted reaction rates define how a single MHC-M interacts with actin, and are supported by single molecule laser trap measurements. Second, the model predicts that when F-V is measured with a quick release instead of an afterload protocol, the transient response should yield a slower velocity for squirrel muscle but not for rat: this is supported by additional muscle experiments. In summary, squirrel jaw muscle can be slow or fast depending on activation details, and muscle F-V measurements are not necessarily linked directly to steady-state cross-bridge kinetics.
Walcott et al. (Sun,) studied this question.