Ca(2+) regulation of contraction in vertebrate striated muscle is exerted primarily through effects on the thin filament, which regulate strong cross-bridge binding to actin. Structural and biochemical studies suggest that the position of tropomyosin (Tm) and troponin (Tn) on the thin filament determines the interaction of myosin with the binding sites on actin. These binding sites can be characterized as blocked (unable to bind to cross bridges), closed (able to weakly bind cross bridges), or open (able to bind cross bridges so that they subsequently isomerize to become strongly bound and release ATP hydrolysis products). Flexibility of the Tm may allow variability in actin (A) affinity for myosin along the thin filament other than through a single 7 actin:1 tropomyosin:1 troponin (A(7)TmTn) regulatory unit. Tm position on the actin filament is regulated by the occupancy of NH-terminal Ca(2+) binding sites on TnC, conformational changes resulting from Ca(2+) binding, and changes in the interactions among Tn, Tm, and actin and as well as by strong S1 binding to actin. Ca(2+) binding to TnC enhances TnC-TnI interaction, weakens TnI attachment to its binding sites on 1-2 actins of the regulatory unit, increases Tm movement over the actin surface, and exposes myosin-binding sites on actin previously blocked by Tm. Adjacent Tm are coupled in their overlap regions where Tm movement is also controlled by interactions with TnT. TnT also interacts with TnC-TnI in a Ca(2+)-dependent manner. All these interactions may vary with the different protein isoforms. The movement of Tm over the actin surface increases the "open" probability of myosin binding sites on actins so that some are in the open configuration available for myosin binding and cross-bridge isomerization to strong binding, force-producing states. In skeletal muscle, strong binding of cycling cross bridges promotes additional Tm movement. This movement effectively stabilizes Tm in the open position and allows cooperative activation of additional actins in that and possibly neighboring A(7)TmTn regulatory units. The structural and biochemical findings support the physiological observations of steady-state and transient mechanical behavior. Physiological studies suggest the following. 1) Ca(2+) binding to Tn/Tm exposes sites on actin to which myosin can bind. 2) Ca(2+) regulates the strong binding of M.ADP.P(i) to actin, which precedes the production of force (and/or shortening) and release of hydrolysis products. 3) The initial rate of force development depends mostly on the extent of Ca(2+) activation of the thin filament and myosin kinetic properties but depends little on the initial force level. 4) A small number of strongly attached cross bridges within an A(7)TmTn regulatory unit can activate the actins in one unit and perhaps those in neighboring units. This results in additional myosin binding and isomerization to strongly bound states and force production. 5) The rates of the product release steps per se (as indicated by the unloaded shortening velocity) early in shortening are largely independent of the extent of thin filament activation ([Ca(2+)]) beyond a given baseline level. However, with a greater extent of shortening, the rates depend on the activation level. 6) The cooperativity between neighboring regulatory units contributes to the activation by strong cross bridges of steady-state force but does not affect the rate of force development. 7) Strongly attached, cycling cross bridges can delay relaxation in skeletal muscle in a cooperative manner. 8) Strongly attached and cycling cross bridges can enhance Ca(2+) binding to cardiac TnC, but influence skeletal TnC to a lesser extent. 9) Different Tn subunit isoforms can modulate the cross-bridge detachment rate as shown by studies with mutant regulatory proteins in myotubes and in in vitro motility assays. (ABSTRACT TRUNCATED)

https://www.physiology.org/doi/pdf/10.1152/physrev.2000.80.2.853

Regulation of Contraction in Striated Muscle

Publisher Summary This chapter focuses on the computer programs for calculating total from specified free, or free from specified total ionic concentrations in aqueous solutions containing multiple metals and ligands. Many experiments in biology, biochemistry, biophysics, and physiology require aqueous solutions with concentrations of free cations, far below those obtainable by simply adding the corresponding salts to the solutions. Then metal buffers made up of the metallic ion (or cation) and the appropriate ligand (or anion) must be used. Similarly, living cells contain ligands, such as cation-binding proteins, that cause the total to differ from the free concentrations of metals. Ligands also bind hydrogen ions so that instead of a single complex between metal and ligand, several complexes form, corresponding to various degrees of protonation. Each has its own stability constant. Thus, apparent stability constants (K app ) have to be calculated to characterize the multiple equilibria among one metal, one ligand, and the hydrogen ion at a given pH value. The main thrust of the present chapter is to describe a FORTRAN program named "SPECS" in such a way that it can be readily used by the largest number of investigators possible.

Computer programs for calculating total from specified free or free from specified total ionic concentrations in aqueous solutions containing multiple metals and ligands.

Skeletal muscle adaptability : Significance for metabolism and performance

On the mechanism of water holding in meat: The swelling and shrinking of myofibrils

The sections in this article are:


1
Motor Unit
1.1
Fibers per Motor Unit

1.2
Contractile Properties

1.3
Biochemical Basis for Differences in Twitch Properties

1.4
Histochemical Differentiation of Muscle Fibers

1.5
Ultrastructural Basis for Skeletal Muscle Fiber Typing

1.6
Maximal Contractile Force

1.7
Speed of Contraction

1.8
Fatigue Characteristics

1.9
Metabolic Characteristics

1.10
Ionic Composition of Skeletal Muscle

1.11
Summary




2
Muscle Fiber Composition in Human Skeletal Muscle

3
Motor-Unit Recruitment

4
Adaptive Response in Skeletal Muscle
4.1
Muscle Size

4.2
Metabolic Capacity




5
Connective Tissue

6
Capillaries
6.1
Methodology

6.2
Anatomy

6.3
Capillary Density

6.4
Capillary Length and Diameter

6.5
Use and Disuse

6.6
Regulation




7
Significance of Adaptation
7.1
Muscular Size

7.2
Substrate Stores

7.3
Enzyme Activities

7.4
Summary

Skeletal Muscle Adaptability: Significance for Metabolism and Performance

A high resolution method for determining the complex stiffness of single muscle fibres is described. In this method the length of the fibre is oscillated sinusoidally, and the resulting force amplitude and phase shift are observed and interpreted in terms of chemo-mechanical energy transduction. In activated, fast skeletal muscles of rabbit (psoas), frog (semitendinosus) and crayfish (walking leg flexor), we resolved at least three exponential rate processes. We named these (A), (B), (C) in order of slow to fast. These processes should reflect ATP hydrolysis and concomitant energy transduction since they are absent in muscles that are relaxed, in rigor or fixed. The great similarities in the complex stiffness data from different muscles suggests that there is a common mechanism of chemo-mechanical energy transduction across a broad phylogenetic range.

Sinusoidal analysis: a high resolution method for correlating biochemical reactions with physiological processes in activated skeletal muscles of rabbit, frog and crayfish.

The attachment to the surface of the ameba (Chaos chaos L. (Pelomyxa carolinensis, Wilson)) of two proteins, ribonuclease and ferritin, and two colloidal suspensions, thorium dioxide and gold, was studied in the electron microscope. The initial step in the pinocytosis of ferritin and thorium dioxide particles by amebas is shown to be the attachment of these substances to the "hairlike" extensions of the plasmalemma. Ribonuclease caused alterations in the structure of the plasmalemma, but on account of its relative lack of density, it could not be definitely localized. Colloidal gold did not appear to be active with respect to pinocytosis in amebas. Since molecules in solution and particles in suspension are taken up by the same mechanism, the first step of which is their attachment to the cell surface, it is suggested that a single mechanism underlies phagocytosis, pinocytosis, ropheocytosis, cytopempsis, and potocytosis.

/pdf/an-electron-microscopic-study-of-pinocytosis-in-ameba-i-the-1i1u0rinkn.pdf

AN ELECTRON MICROSCOPIC STUDY OF PINOCYTOSIS IN AMEBA : I. The Surface Attachment Phase.

Effect of different troponin T-tropomyosin combinations on thin filament activation.

A "skinning%" procedure is described for irreversibly disrupting the sarcolemmal membrane of human skeletal muscle and allowing calcium and other diffusible solutes (such as adenosine triphosphate) access to the myofilament space Single skinned fibers give isometric tensions of about 15 kilograms per square centimeter when exposed to ionized calcium event after 1 to 2 weeks of storage at 5°C For up to 5 days the preparation will sequester and, under appropriate conditions (anion substitution, caffeine addition, or magnesium withdrawal), release calciumn The regulation of intracellular calcium distribution and the calcium-induced activation of the contractile proteins are discussed and related to the morphology of humnan fibers and to similar processes occurring on other muscle preparations

Human skeletal muscle: properties of the "chemically skinned%" fiber.

https://www.cell.com/biophysj/pdf/S0006-3495(07)71052-4.pdf

Philip W. Brandt

Papers

Sinusoidal analysis: a high resolution method for correlating biochemical reactions with physiological processes in activated skeletal muscles of rabbit, frog and crayfish.

AN ELECTRON MICROSCOPIC STUDY OF PINOCYTOSIS IN AMEBA : I. The Surface Attachment Phase.

Effect of different troponin T-tropomyosin combinations on thin filament activation.

Human skeletal muscle: properties of the "chemically skinned%" fiber.

Stiffness and fraction of Myosin motors responsible for active force in permeabilized muscle fibers from rabbit psoas.