Muscle Contraction

Whilst muscular contraction as a ge­ neral phenomenon is familiar through everyday experience, relatively few peo­ ple are aware that it depends on complex interactions between highly ordered polymers of very large molecules (pro­ teins) organized into regular arrays of filaments which slide past each other. It may also come as a surprise to many that the detailed molecular changes that occur during contraction have still not been fully elucidated, although a great deal is now known about many aspects of the process. All muscles are believed to contract by the same basic mechanism, which may also be involved in movement, shape change and internal transport in non­ muscle cells. The muscles which have been studied most extensively are the voluntary, skeletal muscles of verte­ brates. These can generate forces up to 3 kg/cm2 of their cross-section, can shorten by up to a third of their length or more at velocities equivalent to several times their own length per second, and can be switched fully on or fully off in a small fraction of a second, or even within a few milliseconds in some cases. Frogs have been a favourite source of preparations for physiologists, whilst rabbits and chickens have provided most of the material for biochemists. Studies by X-ray diffraction and elec­ tron-microscopy have shown that in these muscles the two principal protein molecules involved in contraction, actin and myosin, are ordered into separate but overlapping arrays of filaments of fixed length (Fig. 1). The myosin fila­ ments form a hexagonal array about 400 A apart, and where overlap occurs, the actin filaments are located symmetrical­ ly between each set of three neighbour­ ing myosin filaments. The space bet­ ween the filaments is occupied by a dilute solution of salts, metabolites and some soluble proteins. Filaments in each array are held in register by cross-con­ necting structures at their mid-points, which form lateral bands known as Zlines (for the actin filaments) and M-lines (for the myosin filaments). The myosin filaments are about 1.5 pm long and have a diameter of 100-150 A, while the actin filaments are somewhat less than 100 A in diameter and extend about 1 pm on either side of the Z-lines. Thus although the filaments themselves are too thin to be resolved in the light microscope, the arrays that they form are readily visible, and the pattern resulting from their partial overlap gives the muscle its characteristic striated ap­ pearance which also shows up par­ ticularly well in electron-micrographs (Fig. 2). Changes in the striation pattern dur­ ing contraction, and the behaviour of the filaments themselves have shown that active shortening of the muscle is brought about by a process in which the actin and myosin filaments slide past each other at essentially constant length. The sliding force is believed to be generated by the action of so-called "crossbridges", which project out side­ ways from the backbone of the myosin filaments and make repetitive attach­ ments to the actin filaments. The cross­ bridges represent the enzymatically ac­ tive part of the myosin molecules, i.e. the part that catalyses the chemical reac­ tion (hydrolysis of adenosine triphosphate-(ATP)) which provides the energy for contraction. Another part of each myosin molecule is built into the back­ bone of the thick filaments, holding the inner ends of the crossbridges in place. Each myosin molecule has a molecular weight of about 5, and the cross­ bridges occur in groups of three at inter­ vals of about 143 A along the thick fila­ ments. A plausible model for the contractile process supposes that upon activation of the muscle (when the arrival of nerve impulses leads to the rapid release of calcium ions throughout the fibres) a crossbridge attaches to actin, under­ goes some structural rearrangement so that it pulls the actin filament along in the appropriate direction for a distance of the order of 40-120 A, and then releases again, returning to its original configuration so that it is ready to begin another cycle. Similar cycles of action are taking place asynchronously at all the other crossbridges within the region of overlap of the actin and myosin fila­ ments and their combined action results in the steady force and shortening gene­ rated by the muscle as a whole. When activation ceases, the crossbridges all detach from actin and the muscle re­ laxes; it can be stretched out to its origi­ nal length by a very small force.