PHYSIOLOGY OF MUSCLES

1. Classification of muscles

The basic function of all types of muscle is to generate force or movement. There are three anatomic types of muscle are skeletal, cardiac, and smooth.

Both skeletal and cardiac muscle are classified microscopically as striated muscle because they have repeating light and dark bands called sarcomeres, in contrast with smooth muscle tissue which does not. Skeletal muscle is also referred to as voluntary because it remains relaxed in the absence of central nerve system stimulation. Cardiac and smooth muscle can function without nerve input and are referred to as involuntary.

2. Neuromuscular junction

Skeletal muscle does not contract until stimulated by action potentials arriving from a motor neuron.

The chemical synapse between a motor neuron and a skeletal muscle cell is called a neuromuscular junction or end plate. Every skeletal muscle cell (fiber) has only one neuromuscular junction, near its midpoint.

As an action potential reaches the end of a motor neuron, voltage-dependent calcium channels open allowing calcium to enter the neuron. Calcium binds to sensor proteins on synaptic vesicles fusion with plasma membrane and subsequent neurotransmitter release from the motor neuron into the synaptic cleft. Motor neurons release acetylcholine, which diffuses through the synaptic cleft and binds nicotinic acetylcholine receptors on the plasma membrane of the muscle fiber. The binding of acetylcholine to the receptor opens Na+ canals and depolarize the muscle fiber, causing a cascade that eventually results in muscle contraction. Acetylcholine within the synaptic cleft is rapidly broken down to choline and acetic acid by the enzyme acetylcholinesterase.

3. Motor unit

Every skeletal muscle cell (fiber) has only one neuromuscular junction, near its midpoint.

Motor neurons branch to activate a group of muscle fibers (they will contract at the same time), known collectively as a motor unit.

Muscles that are subject to fine control (e.g., muscles of the hand, of the face) have many motor units. Therefore, each motor unit is composed of a small number (10-20) of muscle fibers.

Muscles of the limbs or of the back (to bad control) have not a lot motor  units. Therefore, each motor unit is composed of a large number (1000-2000) of muscle fibers.

If a greater force of muscle contraction is needed, the number of active motor neurons increases.

Small motor neurons, which reach only a few muscle fibers, are more excitable than large motor neurons and are recruited first. A weak contraction is produced initially because only a few muscle fibers are contracted.

Large motor neurons are less excitable and require a stronger stimulus from the central nervous system. When large motor neurons are recruited, a large number of muscle fibers are stimulated to produce a strong contraction.

 

Skeletal muscles consist of muscle columns, each of which consists of a bundle of muscle cells (also called fibers or myocytes). Muscle cells are multinucleate and are bounded by the sarcolemma. Each myocyte contains several cylindrical myofibrils, which display a distinctive pattern of light and dark bands under the light microscope.

This striated appearance arises from the orderly arrangement of structural and contractile proteins. Each repeating motif in the striated pattern is called a sarcomere, which is the fundamental contractile unit of skeletal muscle.

 

Each sarcomere has the following elements :

• A Z disk bounds the sarcomere at each end.
• Thin filaments, composed of actin, tropomyosin, and troponins, project from each Z disk.
• Thick filaments, composed of myosin, are present in the center of the sarcomere and are overlapped by thin filaments.
• Sarcomeres line up end-to-end within a single myofibril. The darker areas that can be seen microscopically are denoted as A (anisotropic) bands and correspond to the location of thick filaments. Lighter areas at the ends of sarcomeres are denoted as I (isotropic) bands and correspond to thin filaments.

Thin filaments are composed of actin, with the associated proteins tropomyosin and troponins; thick filaments are composed of myosin. 

The backbone of a thin filament is a double-stranded helix of actin. The helical groove on the actin filament is occupied by tropomyosin. Skeletal muscle contraction is regulated via a protein complex that consists of tropomyosin plus attached troponin subunits. Troponin binds Ca²⁺, which allows muscle contraction to occur. The heads of myosin are cross-bridges that bind to actin during muscle contraction.

4. Sliding filament theory

Steps of Muscle Contraction:

1. Neuron action potential arrives at the end of motor neuron

2. Acetylcholine is released

3. Acetylcholine binds to Nicotinic receptors on motor end plates. This complex opens Sodium canals on the membrane

4. Sodium ions rush into muscle fibers and causes its depolarization

5. Muscle action potential sweeps into T tubules (invaginations of membrane) to activate Sarcoplasmic reticulum

6. Sarcoplasmic reticulum releases calcium ions

7. Calcium binds to troponin to shift Tropomyosin

8. Tropomyosin shift and expose myosin binding site

9. Myosin binds to actin

10. Myosin pivots, pulling actin filaments

11. Myosin releases from actin

12. Myosin re-extends into “ready” position (… and here are steps 9-12, which repeat as long as there is calcium present)

To return a muscle to the relaxed state, Ca²⁺ uptake occurs in the longitudinal tubules via Ca²⁺-pomp (Ca²⁺- ATPases) of the sarcoplasmic reticulum. 

5. Force of contraction

The force of skeletal muscle contraction is controlled by force and frequency of electrical signals from motor nerves to the muscle.

 5.1. The dependence of contraction force from stimulation force.

Different motor units have different excitability. If there is a week stimuli, it causes week contraction because only a few muscle fibers are excitated (contracted). Increasing of the power of stimuli increases power of muscle contraction because more muscle fibers are excited (contracted). So, if a greater force of muscle contraction is needed, the number of active motor neurons increases.

 5.2. The dependence of contraction force from stimulation frequency.

If we stimulate a muscle with a series of electric impulses with long intervals between (less then seven impulses per second), then each impulse causes a single contraction. At high stimulation frequency, the muscle does not have time to relax between stimuli. If each new impulse comes when the muscle is not completely relaxed after the previous contraction, we observe an unfused tetanus. If a subsequent impulse comes at the moment of muscle shortening, we observe a fused or smooth tetanus.

Increased frequency of muscle stimulation (indicated by downward arrows) causes increased force of contraction. At low frequency stimulation, Acetilcholin and Ca²⁺ reuptake is complete and the muscle relaxes completely between stimuli. With high frequency stimulation, Acetilcholin and intracellular Ca²⁺ concentration remains high; the contraction force reaches a maximal plateau - tetanus. So the amplitude of a tetanic contraction is greater than of a single. The effect of increasing force of skeletal muscle contraction is known as temporal summation.

5.3. The dependence of contraction force from Motor unit type.

Motor units vary in size. Muscles that are subject to fine control (e.g., muscles of the hand, of the face) have many motor units. Mainly there are small motor units composed of a small number (10-20) of muscle fibers. Muscles of the limbs or of the back (to bad control) have not a lot motor  units. Mainly there are large motor units composed of a large number (1000-2000) of muscle fibers.

Muscles have different proportions of small and large motor units. Postural muscles contain a higher proportion of small motor units because they must maintain tone and resist fatigue. Large skeletal muscles (biceps and so on) and extraocular muscles are required to make fast, brief movements and therefore contain a high proportion of large motor units .

There are genetic differences in the general proportions of muscle fiber types that are expressed among individuals, which accounts in part for the tendency for a person to be either a better sprinter (more large motor unit) or have higher endurance (more small motor unit).

7. Smooth muscle

Smooth muscle lines the walls of most hollow organs, including organs of the vascular, gastrointestinal, respiratory, urinary, and reproductive systems.

Smooth muscle cells are not striated in appearance (as are skeletal and cardiac muscle) because thin and thick filaments are not organized as sarcomeres . No sarcomeres are present; actin filaments are anchored to dense bodies and overlap myosin in an irregular array; no muscle triads are present.

Excitation contraction coupling in smooth muscle. Ca²⁺ enters the cell from the extracellular fluid via voltage-gated Ca²⁺ channels. Ca²⁺ binds to calmodulin, resulting in activation of myosin which triggers cross-bridge cycling and force development.

An important feature of some smooth muscles (e.g., sphincters) is the ability to maintain force over long periods. The maintenance of muscle tone without high rates of ATP consumption is possible because cross-bridges can remain attached to actin for extended periods.