MUSCLE
Vertebrates have three types of muscle:
Skeletal muscle – Striated, Voluntary
Cardiac muscle – Striated, Involuntary
Smooth (visceral) muscle – Nonstriated, Involuntary
[see Figure] Skeletal muscles typically have fast (phasic) contractions, whereas smooth muscles have slow (tonic) contractions.
[see Figure] Skeletal muscles are attached to either endoskeletons (as in vertebrate limbs) or exoskeletons (as in arthropod limbs). They generally exist in ANTAGONISTIC PAIRS, but sometimes instead counteract the pull of an elastic ligament or of hydrostatic forces (as in spider legs).
[see Figure] Skeletal muscles in vertebrates are typically connected to the bones by collagenous tendons. The anatomical muscle consists of connective tissue plus several hundred to several thousand long cylindrical muscle fibers (cells) arranged into bundles known as fascicles.
[see Figure] Each muscle fiber, in turn, is enclosed in a membrane (SARCOLEMMA) and composed of many MYOFIBRILS surrounded by T-tubules and the membranous SARCOPLASMIC RETICULUM. Most muscle fibers are also richly supplied with MITOCHONDRIA.
[FIG. 9-11b]
[see Figure] The T-tubules (which connect with the sarcolemma) are surrounded by the lateral sacs (Terminal Cisternae) of the sarcoplasmic reticulum. This arrangement is very geometrically regular and repetitive and correlated with the arrangement of MYOFILAMENTS within the myofibrils.
[Fig. 9-11a]
[see Figure] The myofibrils are STRIATED, with alternating dark (= anisotropic or A BANDS) and light (= isotropic or I BANDS). In the center of the A band is a less dense region known as the H ZONE. In the center of each I band is a dense line called a Z LINE (or Z DISK). The repeating unit beween two Z lines is called a SARCOMERE and is the functional unit of the contractile elements of a myofibril.
[see Figure] The striations actually result from the overlapping arrangement of two distinct types of myofilaments: thick filaments and thin filaments. The A band represents the region of thick filaments. The I band represents the region of no thick filaments. The H zone represents the region of no thin filaments.
[Fig. 9-7]
[see Figure] The thick filaments are composed of MYOSIN molecules, which have a club-like head and rod-like tail. The thin filaments are composed primarily of polymers of ACTIN, but also contain the proteins TROPONIN and TROPOMYOSIN.
[see Figure] Cross-sections through myofibrils reveal the highly ordered geometric arrangement of the myofilaments.
[Fig. 9-4]
[see Figure]
Fig. (A) shows portions of several myofibrils. Fig. (B) is an enlarged view of a single sarcomere.
[Fig. 9-3] In addition to the thick and thin filaments, there are large molecules of the elastic protein TITIN, which stretches from Z disk to M line, and of NEBULIN (not shown), which helps to align actin filaments with the Z disk.
[see Figure] When a muscle contracts, the sarcomere, H zone, and I band all decrease in size; however, the A band does not. These observations were the basis for the SLIDING FILAMENT THEORY OF CONTRACTION.
[see Figure] This is a magnified view of the middle region of a sarcomere. Note the cross-bridges between the filaments. Why are there two (instead of one) thin filaments between a pair of track filaments?
[Fig. 9-5]
SLIDING FILAMENT THEORY
The filaments themselves DO NOT contract. Rather, the thick filaments of adjacent sarcomeres slide towards one another between the thin filaments.
The force for this sliding is generated by the CROSS BRIDGES, which are the sites of interaction between the heads of the myosin molecules and the actin filaments. Each cross bridge, energized by the hydrolysis of ATP, rotates on its flexible neck, thereby creating a power stroke and moving the filament.
[Fig. 9-6]
A single cross bridge generates only a tiny force. However, the coordinated movements of large numbers of cross bridges can result in a powerful contraction.
Each cross bridge also moves only a tiny distance. However, the cross bridges sequentially catch, move, release, and repeat this sequence innumerable times in a ratchet-like manner.
The club (head) end of lthe myosin molecule can bind with ATP and also has ATPase activity:
ATP –> ADP + Pi
The hydrolysis of ATP activates the myosin molecule. This occurs before the actual binding of myosin with actin:
M•ATP –> M*.ADP•Pi
Myosin then binds with actin and the stored energy is converted to a cross bridge movement:
A + M*ADP•Pi –> A•M + ADP + Pi
A new molecule of ATP is needed to break the link between actin and myosin:
A•M + ATP –> A ++ M•ATP
[Fig. 9-8]
[see Animation]
[see Figure] A twitch is a much slower response than an action potential and there is a delay (latent period) between the action potential and the twitch.
[Fig. 9-10]
EXCITATION – CONTRACTION COUPLING
An action potential along the muscle membrane is an electrical event, whereas a contraction is a mechanical event.
How is the action potential converted (i.e. transduced) into a mechanical response (i.e. a muscle twitch)?
To understand this, we need to understand the roles of the t-tubules, the sarcoplasmic reticulum, calcium ions, and the troponin and tropomyosin components of the thin filaments.
[See Figure] Under resting conditions, the tropomyosin molecules block the binding sites for actin and myosin, thereby preventing contraction. The troponin molecule, associated with the tropomyosin, contains binding sites for calcium ions.
Calcium ions play a key role in excitation - contraction coupling.
Calcium ions bind with troponin, thereby producing a molecular change, which drags the tropomyosin away from the myosin binding sites on the actin molecules. Myosin can now bind with actin and the muscle can contract.
Removal of calcium ions reverses this process.
[Fig. 9-9]
The calcium is released from the lateral sacs of the sarcoplasmic reticulum in response to an action potential moving inwards via the t-tubules.
After contraction, calcium ions can be actively taken back into the lateral sacs.
[see Animation]
[Fig. 9-12]
Skeletal muscle does not contract spontaneously. Some type of stimulus is required. For the intact muscle, this normally comes from the efferent (motor) neuron.
A single efferent neuron innervates from a few to several hundred individual muscle fibers. A single motor neuron plus all of the muscle fibers that it controls is called a MOTOR UNIT. An entire muscle thus consists, physiologically, of a number of distinct motor units.
[see Figure] Both individual muscle fibers and individual motor units exhibit ALL OR NONE responses. However, an entire muscle does not respond in an all or none fashion.
[Fig. 9-13]
A motor unit consists, functionally, of three separate components: a single efferent neuron, the several muscle fibers that it innervates, and the junctions (synapses) between the neuron and the muscle fibers.
Each of these synapses is called a NEUROMUSCULAR (or MYONEURAL) JUNCTION. The transmitter substance is ACh, which is received at receptor sites on a region of the muscle fiber called the MOTOR END PLATE. These END PLATE POTENTIALS (EPPs) are always excitatory, and a single EPP is adequate to induce an action potential in the muscle fiber. The ACh is inactivated by CHOLINESTERASE.
[Fig. 9-14b]
[FIG. 9-15] The action potential travels, in both directions, from the junction and will then trigger contraction (via excitation - contraction coupling) of the muscle fiber.
[see Animation]
An entire muscle may consist of as few as 10 or as many as 800 or more muscle fibers, arranged into several different motor units. The number of muscle fibers per motor unit can vary greatly, as can the sizes of the different muscle fibers. Smaller motor units are more easily excited than are larger.
The number of motor units activated will depend on the strength of the stimulus. As the stimulus gets stronger, more and more motor units come into play and the force of contraction increases. This is known as RECRUITMENT.
The force exerted by a muscle on an object is called muscle TENSION. The force exerted by the weight of an object attached to a muscle is called the LOAD. These are opposing forces.
If tension > load, the muscle will lift the load
If tension < load, the muscle will not lift the load
There are three more or less distinct types of contraction: isometric, isotonic, and lengthening contraction.
[see Figure] This slide compares two different isometric contractions with an isotonic contraction. Lengthening contraction (not shown) occurs when the weight is stretching a muscle as it contracts.
Work is defined as the product of force times distance. With isometric contractions, there is no distance moved. All of the energy is expressed as HEAT. The energy of isotonic contraction is expressed as WORK and heat.
Physiologists refer to the work associated with lengthening contraction as negative work (physicists, however, stubbornly insist that all work is positive). Lengthening contraction, of course, also involves the liberation of heat.
[see Animation]
[see Figure] This is a set-up for monitoring ISOMETRIC contractions. The muscle is fixed at a set length PRIOR to stimulation.
[see Figure] This is a set-up for monitoring ISOTONIC contractions. The muscle is exposed to an AFTERLOAD (i.e. it is not exposed to the load until it contracts). Note that both length and force change over time and that the force if equal (isotonic) as the load is lifted.
[see Figure] This slide compares four different contractions ranging from a load too heavy to lift (A: isometric) to the lightest load at D.
Note that maximum force is at maximum load, but that maximum velocity is at minimum (i.e. zero) load.
[Fig. 9-18] This slide again illustrates the relationship between load and contraction velocity. The velocity equals zero at maximum isometric tension. If the muscle is afterloaded so that the load can stretch the muscle, however, lengthening velocity will increase as the load progressively exceeds the maximum isometric tension.
[see Animation]
[Fig. 9-19] These are responses of individual muscle fibers. The responses are All or None under a given set of conditions. However, the contractions can be SUMMATED, resulting in a greater tension.
(NOTE: Twitches of an entire muscle are not All or None due to muscle fiber (or motor unit in an IN VIVO muscle) recruitment. We can still observe summation of maximal twitches to yield a supramaximal respoonse).
[see Figure] A TETANUS is a sustained summated contraction. A tetanic contraction can be either complete (fused) or incomplete (unfused). Prolonged tetanus can result in a decrease in tension (i.e. FATIGUE).
[Fig. 9-20]
Tetanic tension may to 3 or more times greater than twitch tension. How can this be if twitch tension is All or None?
Two factors account for the marked increase in tension during tetanus:
(1). In addition to the contractile elements, muscles contain both parallel and series ELASTIC elements. Much of the energy of a single twitch goes to prestretch the series elastic elements.
(2). The concentration of calcium ions progressively increases with each stimulation of the muscle fibers if these occur in rapid sequence. This allows more and more cross-bridge interactions between myosin and actin, thereby achieving the maximum possible tension.
[see Figure] This slide uses springs to diagrammatically represent the elastic components. This depicts an isotonic contraction. However, note that the initial shortening of the contractile elements serves only to stretch the series elastic elements. Therefore, an isotonic contraction has an initial isometric component.
[see Figure] In a pure isometric contraction, there is no movement of the load, but there is still stretching of the series elastic elements.
[see Figure] As noted earlier, an isotonic contraction has an initial isometric component.
[see Figure] Tension vs. Length: The contractile elements can generate the most tension when there is an optimum overlap between the thick and thin filaments. This ordinarily occurs at or near the resting length for the muscle.
NOTE: the elastic elements generate a passive tension opposing excessive stretching or shortening of the muscle.
[Fig. 9-21]
[see Animation]
[see Figure] Most vertebrate skeletal muscles operate over only a rather narrow range of sarcomere lengths (averaging about 36% of optimal length).
There is, however, a great deal of variation among species, and among muscles within a species.
[see Figure] Muscle work is the product of load and the distance that load is moved. There is no work with zero load, and there is no work if the muscle cannot move the load (i.e. isometric conditions). Work is typically maximal at about 40% of maximum load.
There is a relationship between the amount of work a muscle can produce and its size.
Maximum force is directly related to cross-sectional area of a muscle (i.e. the number of myofilaments contributing).
Maximum distance is directly related to length (i.e. a muscle twice as long can contract twice as far).
Therefore, the product of force times distance is proportional to cross-sectional area times length (which is approximately equal to muscle volume).
Although work is more or less directly related to muscle volume, the same is not necessarily true for POWER. Power is work per unit time. A fast muscle has a greater power output than does a slow muscle of the same size. The muscles of small animals are generally faster than those of their larger relatives.
Muscles can generate impressive amounts of force. It has been estimated that the muscles in an adult human male can collectively generate about 22,000 kg (i.e. nearly 25 tons) of tension.
Vertebrates have different types of muscle fibers – sometimes within the same muscle mass. Three main types:
These large fibers can quickly generate a great deal of tension, but they are also quick to fatigue.
These small fibers are the most frequently recruited and are resistant to fatigue.
These fibers are intermediate in size, tension development, and fatigue resistance.
[see Figure] A representative cross-section through a fish. The red muscle fibers are recruited at all speeds, whereas the white fibers are recruited only at fast swimming speeds. Pink fibers are recruited at intermediate and fast speeds.
[Fig. 9-24] Fast-glycolytic (aka white) fibers depend on glycolysis for ATP generation. They are poorly vascularized, hav few mitochondria, and little MYOGLOBIN. Slow-oxidative (aka red) fibers are just the opposite and depend on oxidative phosphorylation for ATP production.
[Fig. 9-25] This slide compares tension development over time for the three fiber types.
[Fig. 9-26] This slide compares tension development and the sequence of recruitment for motor units consisting of the three fiber types.
[Fig. 9-22] Existing ATP is used first for muscle contraction, followed by the reformation of ATP from CREATINE PHOSPHATE. However, for any activity lasting more than a few seconds, ATP must be formed metabolically (Quickly, but inefficiently, via GLYCOLYSIS, or slowly but efficiently via OXIDATIVE PHOSPHORYLATION.
[see Figure]
MOTOR CONTROL IN ARTHROPODS
Arthropod skeletal muscle fibers have very few motor units. Individual fibers are multineuronal (i.e. innervated by several excitatory neurons (some fast and some slow) and also by inhibitory neurons).
[see Figure] NOTE: For the sake of simplicity, only one motor neuron of each type is shown here.
Some small insects (e.g. midges) beat their wings at frequencies in excess of 1000 Hz. How can this be, when action potentials can not fire at these frequencies?
These insects have ASYNCHRONOUS MUSCLES (i.e. the timing of contraction is unrelated to the timing of neuronal input). Once contractions are initiated, the muscles oscillate at the resonant frequency of the system. Nevertheless, a constant train of motor impulses is needed to maintain the wing beating.
Other insects have SYNCHRONOUS MUSCLES, where there is the usual one-to-one relationship between membrane depolarization and contraction.
[see Figure] Synchronous flight muscles are directly attached to the wings by simple lever arrangements. Asynchronous flight muscles are attached to the roof of the thorax, which clicks back and forth between two stable positions, thereby raising and lowering the wings.
SMOOTH MUSCLE
Smooth muscle cells are spindle-shaped and have a single nucleus. The arrangement of actin and myosin filaments is quite different from that of skeletal muscle.
Tension development is slow, but the contractions can be long lasting and smooth muscle cells can adjust to large changes in length.
[Fig. 9-33] The actin-containing filaments are anchored to cytoplasmic structures called DENSE BODIES. The filaments are arranged diagonally, which results in a shortening as the filaments slide together.
Some smooth muscle is SINGLE UNIT (i.e. electrical activity moves directly from cell to cell via GAP JUNCTIONS, and the entire muscle mass responds as a unit.
Some of the individual cells may act as PACEMAKER cells, which can spontaneously depolarize.
Other smooth muscle masses are MULTIUNIT (i.e. the individual cells respond independently).
[see Figure] This depicts multiunit smooth muscle and its innervation by the autonomic nervous system. There are no specialized motor end-plates. Each axon may contain several swollen regions of neurotransmitter release called VARICOSITIES. Each muscle fiber typically receives dual innervation.
[see Figure] This depicts a single unit smooth muscle. Because of the electrical synapses between cells, innervation can be restricted to only a few muscle fibers.
As in skeletal muscle, calcium ions play a key role in excitation - contraction coupling. The exact mechanism, however, is quite different.
Calcium ions (from either external or internal sources) bind with CALMODULIN in the cytosol. This complex then binds to MYOSIN LIGHT-CHAIN KINASE (MLCK), which then uses ATP to phosphorylate myosin cross-bridges. These bridges bind to actin filaments, resulting in movement and contraction. Removal of calcium allows for relaxation.
[Fig. 9-34]
[Fig. 9-35]
In addition to direct excitation or inhibition by autonomic neurons, smooth muscle contractility can be enhanced or reduced by factors such as hormones, local chemical (e.g. oxygen, specific ions, osmolarity) conditions, and mechanical factors (e.g. stretch).
[see Animation]