Muscle contraction - biochemical mechanisms and theories

A muscle contraction is a key biological process by which animals move by contracting their muscles. Movement is the basic property of living systems. The vital activities like digestion, reproduction, excretion and circulation are all possible by the contraction of muscles.
Muscles are complex biological motors, which convert chemical energy into mechanical work and force. In human beings, muscles constitute 40% of the body. The energy for muscle contraction is obtained from the chemicals adenosine triphosphate (ATP) and creatine phosphate ( CP).

                                          Uses of muscles

Skeletal muscle – skeletal muscle gives shape and structure to the body. It enables animals to maintain erect posture. It brings about movement. It helps the animal to secure food and shelter and escape from danger.It helps to communicate its wishes.

Smooth muscle - Smooth muscle assists breathing movements. It aids in hearing and vision.It helps the processes of digestion, excretion, reproduction and circulation. It helps to propel the digested food, body fluids, glandular secretions and waste products. It pumps blood to all parts of the body.

Characteristics of muscles

•         Excitability - the ability to receive and respond to stimuli.

•         Conductivity - The ability  to receive a stimulus and transmit a wave of excitation (electrochemical activity)

•         Contractility - the ability to shorten forcibly when stimulated.

•         Extensibility - the ability to be stretched or extended.

•         Elasticity - The ability to bounce back to original length

                            Types of muscles

Unstriped or plain muscle – It has elongated spindle shaped muscle fibers with thickened central belly and two pointed terminals. The cytoplasm is granular without any cross striations. A rod like nucleus is placed in the center. Myofibrils are arranged in longitudinal axis. They are found in the alimentary canal, respiratory tract, uterus, urinary bladder, arteries and veins.

Cardiac or heart muscle – heart muscles are branched and form a net work. The two adjacent muscle cells form tight junctions in the form of intercalated discs.They exhibit faint transverse striations. They are innervated by autonomic nerve fibers. The nucleus is round or oval in shape. They have fewer myofibrils with greater amount of sarcoplasm for more storage of glycogen and the sarcolemma is indistinct.

Skeletal or striped or muscle – are complex, elongated, cylindrical and fast moving muscles. They vary considerably in size, shape and arrangements of fibers. The size ranges from the smallest stapedium muscle of the middle ear to larger thigh muscles of the human body. Each fiber is multinucleated with transverse and longitudinal striations. The cytoplasm is composed of myofibrils with many myofilaments. Large number tubules run through sarcoplasm and form sarcoplasmic reticulum. The sarcosomes or mitochondria supply ATP to the myofibrils.

        Light microscopic structure of skeletal muscle

Each muscle fiber  displays  dark anisotropic bands or  A bands and light  isotropic bands or I bands. Each A band has a less denser region called H band or Hensen’s line. In each I band, there is a dense cross line called Z band. The area between two adjacent Z lines is called a sarcomere.

Fibrillar system of skeletal muscle

The myofilaments consist of thick myosin filaments and thin actin filaments and are arranged in an overlapping manner. The myosin filaments bear thick knob like projections called cross bridges. The sarcoplasmic reticulum is made up of longitudinal system of canals between myofilaments. There is also T system of canals.

                          Chemical composition of muscle

Water - Muscle contains about 75-80% of water. Water provides a good medium for inorganic and organic compounds. Water reduces friction and dehydration of muscles during contraction.

Proteins - Muscle consists of 3 types of proteins namely structural proteins (e.g., collagen, elastin), contractile proteins (e.g., myosin, actin, and tropomyosin) and enzymatic proteins (e.g., adenosine triphosphatase, creatine phosphatase and lactic dehydrogenase).

Minerals - Calcium ions of sarcoplasm initiates muscle contraction. Magesium ions never initiate muscle contraction but important for muscle coordination. Sodium and Potassium ions set the action potential of impulse conduction.

Organic compounds - Muscle is a storehouse of glycogen and oxidation of glycogen provides energy.  The lipids found in the form of phospholipids. The activity of muscle is proportional to the amount of phospholipids. ATP is the primary source of energy for muscle contraction. ATP molecules found associated with G-actin.

Contractile proteins- Myosin is the  prime contractile element of muscle. It has a triple helical structure. Its molecular weight is 420,000. The hydrolysis of myosin with enzyme trypsin yields two fractions – heavy meromyosin (HMM) and light meromyosin (LMM). Hmm acts as an enzyme ATPase for splitting of ATP into ADP and Pi. The hydrolysis of HMM with papain yields sub- fragment 1 and sub-fragment 2.

Actin -  is non-contractile and elastic in nature. Actin is made up of spherical molecules (G-actin) with a molecular weight  of 60,000. G-actin polymerizes into double stranded helices called fibrous or F-actin.

G-actin +ATP -àF-actin +ADP +Pi.

           Association and disassociation of actomyosin

1 mole of actin +3 mole of myosin -à actomyosin (super- precipitation).

Actomyosin +ATP—^{ca++, mg++}àactin +myosin +ADP

Tropomyosin – is a non-contractile, fibrous protein. It plays important role in sensitizing actin and myosin molecules to calcium ions. This sensitivity is important in order to switch contraction on or off.
Troponin - Troponin occurs at intervals on the actin filament. Troponin takes up ca++ ions from the sarcoplasm to initiate muscle contraction. In muscle troponin and tropomyosin combines to form troponin- tropomyosin system.

Sources of chemical energy

Adenosine triphosphates (ATP) - ATP is the immediate source of energy for muscle contraction. The breakdown of phosphate bond  of ATP releases maximum energy.

Anaerobic glycolysis:

Glucose -à 2 moles of lactic acid +8ATPs.

Aerobic glycolysis coupled with Kreb‘s cycle:

Glucose --à6 CO2 + 6H2O +38 ATPs.

Creatine phosphate (CP) or phosphagen - It forms a reservoir of high energy phosphate in the muscle.It cannot be used as a direct source of energy. It can be used for regeneration of ATP from ADP.

Creatine phosphate----------àcreatine + phosphoric acid

Phosphoric acid +ADP -------à ATP

Glucose – glycolysis as a source of energy - Glucose is stored in the muscle in the form of glycogen. Muscle glycogen is converted into glucose by glycogenolysis. Glucose is oxidized by glycolysis.

C⁶H¹²O⁶   + 6O²--------à6CO² +6H²O +38 ATP

Cori’s Lactic acid cycle

The oxidation of lactic acid to carbon dioxide produces energy for the reconversion of ADP to ATP. The lactic acid produced in the muscle contraction passes into blood stream and is transported to the liver. Within the liver, lactic acid is converted to liver glycogen and then to blood glucose. The conversion of lactic acid to glycogen requires oxygen. Muscle glycogen comes only from the glucose of the blood.

Biochemical basis of muscle stimulation

The stimulation of nerve from the central nervous system initiates electrical changes in the muscle. The depolarization of sarcolemma is caused by the sudden influx of Na+ ions and efflux of k+ ions. The nerve impulse spreads in the muscle and releases Ca2+ ions from the sarcoplasmic reticulum. The flooding of Ca2+ ions starts the contractile machinery.

       Molecular changes during muscle contraction
The Ca2+ ions bind to the troponin molecules. Troponin – Ca2+ complex removes tropomyosin blockage of actin sites. The heads of myosin – ATP complex form Cross-bridges to actin filament. The hydrolysis of ATP induces conformational changes in the heads of myosin.
1 mole of Actin + 3 moles of myosin à Actomyosin

       Molecular changes during muscle relaxation –

The Ca2+ ions are sequestered from actin filament by sacroplasmic reticulum. The Ca2+ ions are released from troponin – Ca2+ complex. Troponin permits tropomyosin return to blocking position. Then there is a separation of myosin-actin cross-bridges. ATP – myosin Complex reformed in heads of thick filament.

Physical changes during muscle contraction
Heat production -liberation of heat is always associated with muscle contraction.

Electricity generation -small amount of electrical energy is released.

Volume changes –negligible changes in volume occur.

Change in optical properties -changes in the birefringence and transparency occur at the muscle fiber.

Sound production -muscle sound noted during contraction.

Theories/ models  of muscle contraction

Sliding filament theory 

This theory was evolved independently and more or less simultaneously by A.F Huxley and H.E. Huxley around 1950s. According to this theory, the force of contraction is developed by the cross bridges in the overlap region. The active shortening is caused by the movement of the cross bridges, which causes one filament to slide over the other. During muscle contraction, the actin filaments alone show movement. But the myosin filaments remain static. The mechanical movement utilizes the energy derived from the breakdown of ATP molecules.

 Electrochemical theory – Davies model (1963)
 In the resting state, the cross        bridges are in slanting position due to negative charges in both the basal and tips of cross bridges due to the concentration of magnesium ions. After the stimulation of muscle, the release of calcium ions change the electrical character which leads to mutual repulsion and shortening of the cross bridges. The attachment of cross bridges on the actin filaments cause sliding of actin filaments while myosin filaments remain static.

Rowboat model- Huxley-Simmons model – According to this scheme, there are flexible hinges on myosin: one between S1 heads and the long rods and the second between S2 and the LMM at the trypsin reaction site. When the head piece (S1) binds to the exposed site on actin it is thought to rotate. This type of rotation occurs simultaneously at numerous locations of actin – myosin filaments which cause shortening of the muscle. The energy for this process derived from the hydrolysis of ATP.