Distributed Representations for Actin-Myosin Interaction in the Oscillatory Contraction of Muscle

Abstract

In this paper we suggest and test a specific hypothesis relating the attachment-detachment cycle of cross bridges between actin (I) and myosin (A) filaments to the measured length-tension dynamics of active insect fibrillar flight muscle. It is first shown that if local A-filament strain perturbs the rate constants in the cross-bridge cycle appropriately, then exponentially delayed tension changes can follow imposed changes of length; the latter phenomenon is sufficient for the work-producing property of fibrillar muscle, as measured with small-signal forcing of length and at low Ca(2+) concentration, and possibly for related effects described recently in frog striated muscle. It is not clear a priori that the above explanation of work production by fibrillar muscle will remain tenable when the viscoelastic complexity of the heterogeneous sarcomere is taken into account. However, White's (1967) recent mechanical and electron microscope study of the passive dynamics of glycerinated fibrillar muscle has produced a model of the distributed viscoeleastic structure sufficiently explicit that alternative schemes for cross-bridge force generation in this muscle can now be tested more critically than previously. Therefore, we derive and solve third-order partial-differential equations which relate local interfilament shear forces associated with the perturbed cross-bridge cycles to the over-all length-tension dynamics of an idealized sarcomere. We then show (a) that the starting hypothesis can account approximately for the small-signal dynamics of glycerinated muscle in the work-producing state over two decades of frequency and (b) that the rate constants for cross-bridge formation and breakage, restricted solely by fitting of the model to the mechanical data, determine a cycling rate of cross bridges in the model compatible with recent measurements of ATP hydrolysis rate vs. stretch in this muscle. Finally, the formulation is extended tentatively to the large-signal nonlinear case, and shown to compare favorably with previous suggestions for the origin of the work-producing dynamics of fibrillar flight muscle.

X-ray diffraction evidence for myosin-troponin connections and tropomyosin movement during stretch activation of insect flight muscle

“…Proposed mechanisms for the 60-y mystery of stretch activation have included helical matching between thick and thin filaments (34,35), lattice spacing changes (36), stress-induced changes in myosin activity (14,(37)(38)(39), and stress-induced changes in thinfilament activation (12,(40)(41)(42). We favor the last mechanism, and our results, particularly the time-resolved sequence of tropomyosin movement, cross-bridge binding and force production, strongly support the hypothesis that steric blocking-unblocking by tropomyosin regulates stretch activation.…”

Mechanism of force generation by myosin heads in skeletal muscle

“…We used a distributed filament compliance formalism 21,29,30 to calculate the force and strain distribution along the myosin and actin filaments. The strain in myosin heads during isometric contraction was assumed to be uniform along the filament overlap zone.…”

Ultrastructural and molecular analyses of homozygous-viable Drosophila melanogaster muscle mutants indicate there is a complex pattern of myosin heavy-chain isoform distribution.

“…This muscle has evolved many special fea tures (Shafiq 1963a,b;Smith 1963;Garamvolgyi 1965a,b;Peristianis and Gregory 1970;Cullen 1974;Crossley 1978) that allow it to produce high wing beat frequencies. The IFM also is unique because it displays asynchronous contraction, where a single burst from motor neurons causes activation that is maintained by rapid changes in length and tension, resulting from the mechanical properties of the muscle (Nachtigal and Wilson 1967;Pringle 1967;Thorson and White 1969;Tregear 1975). The IFM is called fibrillar because the muscle cells contain large numbers of discrete cylin drical myofibrils that can be teased individually away during dissection.…”