title: Two-state model of acto-myosin attachment-detachment predicts C-process of sinusoidal analysis.
abstract: The force response of activated striated muscle to length perturbations includes the so-called C-process, which has been considered the frequency domain representation of the fast single-exponential force decay after a length step (phases 1 and 2). The underlying molecular mechanisms of this phenomenon, however, are still the subject of various hypotheses. In this study, we derived analytical expressions and created a corresponding computer model to describe the consequences of independent acto-myosin cross-bridges characterized solely by 1), intermittent periods of attachment (t(att)) and detachment (t(det)), whose values are stochastically governed by independent probability density functions; and 2), a finite Hookian stiffness (k(stiff)) effective only during periods of attachment. The computer-simulated force response of 20,000 (N) cross-bridges making up a half-sarcomere (F(hs)(t)) to sinusoidal length perturbations (L(hs)(t)) was predicted by the analytical expression in the frequency domain, (F(hs)(omega)/L(hs)(omega))=(t(att)/t(cycle))Nk(stiff)(iomega/(t(att)(-1)+iomega)), where t(att) = mean value of t(att), t(cycle) = mean value of t(att) + t(det), k(stiff) = mean stiffness, and omega = 2pi x frequency of perturbation. The simulated force response due to a length step (L(hs)) was furthermore predicted by the analytical expression in the time domain, F(hs)(t)=(t(att)/t(cycle))Nk(stiff)L(hs)e(-t/t(att)). The forms of these analytically derived expressions are consistent with expressions historically used to describe these specific characteristics of a force response and suggest that the cycling of acto-myosin cross-bridges and their associated stiffnesses are responsible for the C-process and for phases 1 and 2. The rate constant 2pic, i.e., the frequency parameter of the historically defined C-process, is shown here to be equal to t(att)(-1). Experimental results from activated cardiac muscle examined at different temperatures and containing predominately alpha- or beta-myosin heavy chain isoforms were found to be consistent with the above interpretation.
authors.affiliation: Department of Molecular Physiology and Biophysics, University of Vermont, Burlington, Vermont, USA. palmer@physiology.med.uvm.edu
authors.forename: Bradley M
authors.initials: BM
authors.lastname: Palmer
authors.forename: Takeki
authors.initials: T
authors.lastname: Suzuki
authors.forename: Yuan
authors.initials: Y
authors.lastname: Wang
authors.forename: William D
authors.initials: WD
authors.lastname: Barnes
authors.forename: Mark S
authors.initials: MS
authors.lastname: Miller
authors.forename: David W
authors.initials: DW
authors.lastname: Maughan
mesh_terms: D000205:Actomyosin / Q000378:metabolism*; D003198:Computer Simulation; D004548:Elasticity; D007700:Kinetics; D008954:Models, Biological; D018482:Muscle, Skeletal / Q000033:anatomy & histology / Q000502:physiology; D009218:Myosins / Q000737:chemistry / Q000378:metabolism; D011336:Probability; D011485:Protein Binding; D012518:Sarcomeres / Q000648:ultrastructure; D014584:User-Computer Interface
chemical_list: D000205:Actomyosin; D009218:Myosins