  Calcium activation of striated muscle is known to exhibit a strongly
cooperative dependency on calcium. Because the calcium receptor protein,
troponin (Tn) is known to bind calcium non-cooperatively and has yet to be
linked to a cooperative change in the myosin-blocking protein, tropomyosin
(Tm), we describe a model in which cooperativity is exclusively a
myosin-dependent mechanism. The model couples the energies of three
well-described reactions with actin, namely, actin-Tn, actin-Tm, and
actin-Tm-myosin, to the well-documented positions of Tm, B (blocking), C
(central), and M (myosin-dependent) respectively. Results of simulations with
and without data are consistent with a strand of Tm composed of ~20 subunits
being moved by the concerted action of 3-5 myosin heads resulting in an
all-or-none activation of the entire region of the thin filament overlapped by
myosin. Equations derived from the model fit both equilibrium myosin binding
data and steady-state calcium-dependent tension data and simulate
non-cooperative calcium binding both in the presence and absence of myosin. All
parameters of the model can be determined experimentally. The mechanism is
consistent with steric blocking being both necessary and sufficient for
regulation of striated muscle and can be applied to any actin-based contractile
system that includes Tm and filamentous myosin.
