Muscle Physiology PDF

MUSCLE PHYSIOLOGY Dr. Om Perkash Sr. Lecturer Dadabhoy Institute of Higher Education OBJECTIVES: At the end of the lecture, students will be able to learn: Physiological structure of muscle. Skeletal muscle contraction. Skeletal, smooth and cardiac muscle contractio...

MUSCLE PHYSIOLOGY Dr. Om Perkash Sr. Lecturer Dadabhoy Institute of Higher Education OBJECTIVES: At the end of the lecture, students will be able to learn: Physiological structure of muscle. Skeletal muscle contraction. Skeletal, smooth and cardiac muscle contraction. Neuromuscular junction and transmission. Excitation contraction coupling. Structure and function of motor unit.  PHYSIOLOGICAL STRUCTURE OF MUSCLE  Muscle mass is separated from the neighboring tissues by a thick fibrous tissue layer known as fascia. Beneath the fascia, muscle is covered by a connective tissue sheath called epimysium. In the muscle, the muscle fibers are arranged in various groups called bundles or fasciculi. Connective tissue sheath that covers each fasciculus is called perimysium. Each muscle fiber is covered by a connective tissue layer called the endomysium as shown in following figure.  MUSCLE FIBER Each muscle cell or muscle fiber is cylindrical in shape. Average length of the fiber is 3 cm. It varies between 1 cm and 4 cm, depending upon the length of the muscle. The diameter of the muscle fiber varies from 10 μ to 100 μ. The diameter varies in a single muscle. Muscle fibers are attached to a tough cord of connective tissue called tendon. Tendon is in turn attached to the bone. Each muscle fiber is enclosed by a cell membrane called plasma membrane, that lies beneath the endomysium. It is also called sarcolemma as shown in figure. Cytoplasm of the muscle is known as sarcoplasm. Structures embedded within the sarcoplasm are: 1. Nuclei 2. Myofibril 3. Golgi apparatus 4. Mitochondria 5. Sarcoplasmic reticulum 6. Ribosomes 7. Glycogen droplets 8. Occasional lipid droplets. MYOFIBRIL Myofibrils or myofibrillae are the fine parallel filaments present in sarcoplasm of the muscle cell. Myofibrils run through the entire length of the muscle fiber. In the cross-section of a muscle fiber, the myofibrils appear like small distinct dots within the sarcoplasm. Diameter of the myofibril is 0.2 to 2 μ. The length of a myofibril varies between 1 cm and 4 cm, depending upon the length of the muscle fiber. MICROSCOPIC STRUCTURE OF A MYOFIBRIL Light microscopic studies show that, each myofibril consists of a number of two alternating bands which are also called the sections, segments or disks. These bands are formed by muscle proteins. The two bands are: 1. Light band or ‘I’ band. 2. Dark band or ‘A’ band. Light Band or ‘I’ Band Light band is called ‘I’ (isotropic) band because it is isotropic to polarized light. When polarized light is passed through the muscle fiber at this area, light rays are refracted at the same angle. Dark Band or ‘A’ Band Dark band is called ‘A’ (anisotropic) band because it is anisotropic to polarized light. When polarized light is passed through the muscle fiber at this area, the light rays are refracted at different directions (An = not; iso= it; trops = turning). Dark band is also called ‘Q’ disk (Querscheibe = cross disk).  I band is divided into two portions, by means of a narrow and dark line called ‘Z’ line or ‘Z’ disk (in German, zwischenscheibe = between disks). The ‘Z’ line is formed by a protein disk, which does not permit passage of light. The portion of myofibril in between two ‘Z’ lines is called sarcomere. SARCOMERE Definition Sarcomere is defined as the structural and functional unit of a skeletal muscle. It is also called the basic contractile unit of the muscle. Extent Each sarcomere extends between two ‘Z’ lines of myofibril. When the muscle is in relaxed state, the average length of each sarcomere is 2 to 3 μ. Components Each myofibril consists of an alternate dark ‘A’ band and light ‘I’ band as shown in following figure. In the middle of ‘A’ band, there is a light area called ‘H’ zone (H = hell = light – in German, H = Henson – discoverer). In the middle of ‘H’ zone lies the middle part of myosin filament. This is called ‘M’ line (in German-mittel = middle). ‘M’ line is formed by myosin binding proteins. ELECTRON MICROSCOPIC STUDY OF SARCOMERE Electron microscopic studies reveal that the sarcomere consists of many threadlike structures called myofilaments. Myofilaments are of two types: 1. Actin filaments 2. Myosin filaments. Actin Filaments Actin filaments are the thin filaments with a diameter of 20 Å and a length of 1 μ. These filaments extend from either side of the ‘Z’ lines, run across ‘I’ band and enter into ‘A’ band up to ‘H’ zone. Myosin Filaments Myosin filaments are thick filaments with a diameter of 115 Å and a length of 1.5 μ. These filaments are situated in ‘A’ band. COMPOSITION OF MUSCLE Muscular Contraction The muscle contracts when it is stimulated. Contraction of the muscle is a physical or mechanical event. In addition, several other changes occur in the muscle. ELECTRICAL CHANGES DURING MUSCULAR CONTRACTION Electrical events occur in the muscle during resting condition as well as active conditions. Electrical potential in the muscle during resting condition is called resting membrane potential. Electrical changes that occur in active conditions, i.e. when the muscle is stimulated are together called action potential.  RESTING MEMBRANE POTENTIAL Resting membrane potential is defined as the electrical potential difference (voltage) across the cell membrane (between inside and outside of the cell) under resting condition. It is also called membrane potential, transmembrane potential, transmembrane potential difference or transmembrane potential gradient. There is negativity inside and positivity outside the muscle fiber. This potential difference is constant and is called resting membrane potential. The condition of the muscle during resting membrane potential is called polarized state. In human skeletal muscle, the resting membrane potential is –90 mV. ACTION POTENTIAL Action potential is defined as a series of electrical changes that occur in the membrane potential when the muscle or nerve is stimulated. Action potential occurs in two phases: 1. Depolarization 2. Repolarization. Depolarization Depolarization is the initial phase of action potential in which inside of the muscle becomes positive and outside becomes negative. That is, the polarized state (resting membrane potential) is abolished resulting in depolarization. Repolarization Repolarization is the phase of action potential in which the muscle reverses back to the resting membrane potential. That is, within a short time after depolarization the inside of muscle becomes negative and outside becomes positive. So, the polarized state of the muscle is reestablished. Ionic Basis of Action Potential Voltage gated Na+ channels and the voltage gated K+ channels play important role in the development of action potential. During the onset of depolarization, voltage gated sodium channels open and there is slow influx of Na+. When depolarization reaches 7 to 10 mV, the voltage gated Na+ channels start opening at a faster rate. It is called Na+ channel activation. When the firing level is reached, the influx of Na+ is very great and it leads to overshoot.  But the Na+ transport is short lived. It is because of rapid inactivation of Na+ channels. Thus, the Na+ channels open and close quickly. At the same time, the K+ channels start opening. This leads to efflux of K+ out of the cell, causing repolarization.  Neuromuscular Junction DEFINITION Neuromuscular junction is the junction between terminal branch of the nerve fiber and muscle fiber. STRUCTURE Skeletal muscle fibers are innervated by the motor nerve fibers. Each nerve fiber (axon) divides into many terminal branches. Each terminal branch innervates one muscle fiber through the neuromuscular junction as shown in following figure. Axon Terminal and Motor Endplate Terminal branch of nerve fiber is called axon terminal. When the axon comes close to muscle fiber, it loses the myelin sheath. So, the axis cylinder is exposed. This portion of the axis cylinder is expanded like a bulb, which is called motor endplate. Axon terminal contains mitochondria and synaptic vesicles. Synaptic vesicles contain the neurotransmitter substance, acetylcholine (Ach). The Ach is synthesized by mitochondria present in the axon terminal and stored in the vesicles. Mitochondria contain ATP, which is the source of energy for the synthesis of acetylcholine. Synaptic Trough or Gutter Motor endplate invaginates inside the muscle fiber and forms a depression, which is known as synaptic trough or synaptic gutter. The membrane of the muscle fiber below the motor endplate is thickened. Synaptic Cleft Membrane of the nerve ending is called the presynaptic membrane. Membrane of the muscle fiber is called postsynaptic membrane. Space between these two membranes is called synaptic cleft. Synaptic cleft contains basal lamina. It is a thin layer of spongy reticular matrix through which, the extracellular fluid diffuses. An enzyme called acetylcholinesterase (AchE) is attached to the matrix of basal lamina, in large quantities. Subneural Clefts Postsynaptic membrane is the membrane of the muscle fiber. It is thrown into numerous folds called Sub-neural clefts. Postsynaptic membrane contains the receptors called nicotinic acetylcholine receptors as shown in following figure. NEUROMUSCULAR TRANSMISSION Neuromuscular transmission is defined as the transfer of information from motor nerve ending to the muscle fiber through neuromuscular junction. It is the mechanism by which the motor nerve impulses initiate muscle contraction. Events of Neuromuscular Transmission A series of events take place in the neuromuscular junction during this process as shown in following figure. The events are: 1. Release of acetylcholine 2. Action of acetylcholine 3. Development of endplate potential 4. Development of miniature endplate potential 5. Destruction of acetylcholine. 1. RELEASE OF ACETYLCHOLINE When action potential reaches axon terminal, it opens the voltage-gated calcium channels in the membrane of axon terminal. Calcium ions from extracellular fluid (ECF) enter the axon terminal. These cause bursting of the vesicles by forcing the synaptic vesicles move and fuse with presynaptic membrane. Now, acetylcholine is released from the ruptured vesicles. By exocytosis, acetylcholine diffuses through the presynaptic membrane and enters the synaptic cleft. Each vesicle contains about 10,000 acetylcholine molecules. And, at a time, about 300 vesicles open and release acetylcholine. 2. ACTION OF ACETYLCHOLINE After entering the synaptic cleft, acetylcholine molecules bind with nicotinic receptors present in the postsynaptic membrane and form acetylcholine- receptor complex. It increases the permeability of postsynaptic membrane for sodium by opening the ligand-gated sodium channels. Now, sodium ions from ECF enter the neuromuscular junction through these channels. And there, sodium ions alter the resting membrane potential and develops the electrical potential called the endplate potential. 3. DEVELOPMENT OF ENDPLATE POTENTIAL Endplate potential is the change in resting membrane potential when an impulse reaches the neuromuscular junction. Resting membrane potential at neuromuscular junction is –90 mV. When sodium ions enter inside, slight depolarization occurs up to –60 mV, which is called endplate potential. 4. DEVELOPMENT OF MINIATURE ENDPLATE POTENTIAL Miniature endplate potential is a weak endplate potential in neuromuscular junction that is developed by the release of a small quantity of acetylcholine from axon terminal. And, each quantum of this neurotransmitter produces a weak miniature endplate potential. The amplitude of this potential is only up to 0.5 mV. Miniature endplate potential cannot produce action potential in the muscle. When more and more quanta of acetylcholine are released continuously, the miniature resulting in action potential in the muscle. 5. DESTRUCTION OF ACETYLCHOLINE Acetylcholine released into the synaptic cleft is destroyed very quickly, within one millisecond by the enzyme, acetylcholinesterase. However, the acetylcholine is so potent, that even this short duration of 1 millisecond is sufficient to excite the muscle fiber. Rapid destruction of acetylcholine has got some important functional significance. It prevents the repeated excitation of the muscle fiber and allows the muscle to relax. Reuptake Process Reuptake is a process in neuromuscular junction, by which a degraded product of neurotransmitter reenters the presynaptic axon terminal where it is reused. Acetylcholinesterase splits (degrades) acetylcholine into inactive choline and acetate. Choline is taken back into axon terminal from synaptic cleft by reuptake process. There, it is reused in synaptic vesicle to form new acetylcholine molecule. Excitation-contraction coupling in skeletal muscle Excitation - contraction coupling in the skeletal muscle is the sequence of events through which the nerve fiber stimulates the skeletal muscle fiber causing its contraction. Motor Unit Single motor neuron, its axon terminals and the muscle fibers innervated by it are together called motor unit. Each motor neuron activates a group of muscle fibers through the axon terminals. Stimulation of a motor neuron causes contraction of all the muscle fibers innervated by that neuron. References K Sembulingam - Essentials of Medical Physiology, 6th Edition.