Specialized proteins in muscle cells are the building blocks of the structures constituting the moving machinery of muscle. They are disposed in myofilaments which are discernible by electron microscopy. These myofilaments are of two kinds, and their regular arrangement within the cell gives the striated pattern to skeletal muscle fibers (see illustration). It is recognized that the sliding of the two sets of filaments relative to each other is the molecular basis of muscle contraction. To understand the ultimate mechanism that causes the movement of these filaments (relative to each other), it is necessary to consider the features of the individual molecules making up these filaments. Evidence has been accumulating that practically all nonmuscle cells, although lacking the filaments of muscle, contain proteins similar to those found in muscle; these proteins are likely to be involved in cell motility and in determining properties of cell membranes.
Banding pattern of a sarcomere, showing arrangement of myosin and actin molecules. A, I, and Z indicate bands.
Molecules of myosin, amounting to about 60% of the total muscle protein, are arranged in filaments occupying the central zone of each segment (sarcomere) or the fibril, the A band. Myosin is an elongated molecule made up of two intertwined heavy peptide chains (molecular weight of about 200,000) whose ends form two separate globular structures. The intertwined portion forms a rigid rod; each of the two globular portions (heads) contains a center capable of combining with, and splitting off, the terminal phosphate of adenosine triphosphate (ATP); ATP is the ultimate source of energy for muscle contraction. Each globular head can combine with actin.
The chief constituent of the filaments originating in the Z band of each sarcomere is actin. Actin filaments are made up of globular units in a double helix; there are 13 to 15 of these units in each strand for every complete turn of this helix.
These two proteins, or rather protein complexes, are associated with the actin filaments. Tropomyosin is an α-helical protein containing two intertwined polypeptide chains that extend over about seven globular actin units. Each tropomyosin molecule is associated with one troponin molecule, which in turn consists of three different types of subunits. In contrast to the tropomyosin molecule, the troponin complex and its subunits are thought to be essentially spherical in shape. Both tropomyosin and troponin are required to make the interaction of actin and myosin sensitive to calcium ions.
A great deal of information has come to light concerning the process by which the interaction between actin and myosin is regulated in the living cell. In higher organisms troponin and tropomyosin participate in this regulation. In the presence of these proteins the combination of actin and myosin cannot take place. However, if a small amount of ionized calcium is present, the inhibitory effect of the tropomyosin-troponin system is reversed, and the interaction withactin and myosin becomes fully effective.
This regulation involves a movement of tropomyosin molecules within the thinfilaments from positions in which they block the combination of actin with themyosin moiety. Within the muscle cell the amount of calcium available isregulated by certain membranous structures, collectively the sarcoplasmicreticulum, that appear to have the ability to store calcium in the restingstate. Upon excitation, the outer membrane of the muscle cell undergoes achange in permeability. This change spreads inside the muscle through theso-called transverse tubular system and causes a release of calcium within thecell. The calcium ions thus released permit the interaction of actin andmyosin, leading to the liberation of chemical energy from ATP and itstransformation into mechanical work. See also Motor systems; Muscle.
