Muscle & Nerve (Excitable Tissues) PDF

Lecturer of Physiology Faculty of Vet. Med. Cairo University  Contents Excitable tissues. Muscles and their types. Structure of skeletal muscles. Changes which occur during muscle contraction include: a-Electrical changes. b-Mechanical changes. c- Metabolic or Chem...

Lecturer of Physiology Faculty of Vet. Med. Cairo University  Contents Excitable tissues. Muscles and their types. Structure of skeletal muscles. Changes which occur during muscle contraction include: a-Electrical changes. b-Mechanical changes. c- Metabolic or Chemical changes. d-Thermal changes. e-Excitability Changes Excitable tissues: tissues which respond to stimuli such as muscles and nerves Nerve: responds by propagation of impulse and release of neurotransmitter. Muscle: responds by contraction. Properties of excitable cell membranes: 1 - The membranes have an electrical excitability across the membrane. (In response to depolarization of the membrane above a certain threshold voltage) and may transmit an impulse along the membrane. 2 - The membranes contain ion channels (pores) that may be opened or closed, allowing specific ions to flow across.  Types of muscles There are three types of muscles : skeletal, cardiac and smooth.  Items Skeletal M Cardiac M Smooth M Structure striated striated non-striated Location skeleton heart visceral organs Activation voluntary involuntary involuntary Function mechanical pump motility work Speed of fast intermediate slow contraction 1- Excitability: the ability of muscle to respond to external stimulus. 2- Conductivity: the ability of transmission of the local excitatory state along the muscle fibers. 3- Contractility: the ability of muscle to be shorten without any change in its external shape or increase in tension. 4- Muscles have the capacity to recover after being stimulated and return to the original form  Skeletal muscles constitute 40-45% of the body weight. They are attached to the skeleton. Function of Skeletal muscles : It is the engine of the body. 1- Mechanical work: Movement of different parts of the body as: Locomotion Posture Respiration Eating 2- Generation of heat: Muscle tone They generate heat for warming the body through the shivering. 3- Storage of fat, protein, glycogen, minerals and vitamins 4- Source of meat for human consumption.  Structure of Skeletal Muscles Each muscle is an organ composed of muscle fibers, blood vessels, nerve fiber and connective tissue (CT) Each muscle fiber is a single, long, cylindrical and multinucleated cell. Muscle fibers (20-40) are grouped into units called muscle bundles Each muscle is enclosed by a sheath of white fibrous CT which aggregates and forms tendon at both ends of the muscle. Muscle CT sheathes are: Epimysium: dense CT surrounds the entire muscle. Perimysium: fibrous CT surrounds groups of muscle fibers (Bundle or Fasiculus) Endomysium: fine sheath of CT surrounds each muscle fiber  The muscle fiber has a thin elastic wall (Sarcolemma)”plasma membrane” which contains the following: Nuclei: situated in the periphery of the fiber. Sarcoplasm: it is the cytoplasm which contains myofibrils, mitochondria, sarcoplasmic reticulum, myoglobin, glycogen granules& fat droplets.  Muscle fibers contains several hundred to several thousand myofibrils arranged in parallel along its length. Myofibril are densely packed rod -like contractile elements. Each myofibril is composed of actin (thin) and myosin (thick) filaments, repeated in units called sarcomeres, which are the basic functional units of the muscle fiber Myofibrils consist of a repeating series of : 1- Dark A bands: contain both actin and myosin and gives a complex response to polarized light (Anisotropic, double reflection). 2- Light I bands: contain only actin so gives a simple response to polarized light (Isotropic or same reflection).  The arrangement of the A and I bands are perpendicular on the long axis of the fiber is responsible striation The length of A band is 1.5µm and I band is 0.8µm. H- zone (hells) is a light zone in the middle of A band. No overlapping of actin and myosin  In the center of H- zone is the M line ( from the German mitte ,middle ) which appears darker due to the presence of the protein desmin and contains enzyme like creatine phosphokinase, which is important in the energy metabolism related to muscle contraction. Z- line or disk (zwischenschelbe = central membrane) is a dark zone in the middle of the I band.  The region of myofibril between 2 successive Z discs The sarcomere is the functional unit of muscle where contraction and relaxation occur.  Molecular structure of myofibril Myofibril is constructed from two types of filaments: 1- Thin filaments of 2µm relaxed length. It extend across I band and partway into A band. 2- Thick filaments of 1.5µm relaxed length. It extend the entire length of A band.  The dark A band is composed of thin and thick filaments but the light I band composed of thin filament.  Thick filament Thick filaments are composed of the protein myosin. The myosin filament is composed of 100 pair of myosin molecules (50 pair in each direction). The shape of myosin molecule is similar to a golf club with two heads.  Each myosin molecule is composed of 2 parts: Tail Heads Half of the myosin heads angle to the left and half of them angle to the right creating an area in the middle of the filament known as the bare zone. Myosin molecule consists of: tail and heads Tail: Two polypeptide chains in a double helical form. Forms the core or body of myosin filament. Heads: consists of 2 parts: A) Cross bridge (S1, Subfragment 1) “globular heads” Characterized by 2 sites: Actin binding site ATP binding site : binding of ATP, ATPase activity & transfer energy to cross bridge for muscle contraction B)Double helix (Subfragment 2, S2) Emerge from the body of myosin filament Characterized by 2 hinges: At connection of tail and head providing vertical movement so the cross bridge can bind to actin At connection of cross bridge and double helix providing back and forth movement called “power stroke” Thin filaments are composed of: Actin Tropomyosin Troponin  Actin is the major component of the thin filament. Actin molecule is a double helix ( filamentous or F-actin) which is composed of small globular subunits called globular actin (G- actin). The subunits contain active sites for binding myosin cross bridge. The binding sites have ATPase activity.  It is the regulatory protein in the form of a double helical rod shape of two polypeptide chain. It covers the actin binding sites at resting state and acts as a binding site for troponin.  It is a complex molecule of the three globular subunits: 1-Troponin T : bind to tropomyosin 2-Troponin C: bind to calcium 3-Troponin I: bind to actin and inhibit the binding of actin and myosin.  Sarcoplasmic reticulum (SR) Sarcoplasmic reticulum is a smooth endoplasmic reticulum that surrounds the myofibrils. It regulates the intracellular calcium level by calcium ATP pump. It is composed of paired terminal cisternae and longitudinal tubules.  Transverse tubules (T - tubules) Transverse tubules (T- tubules) are invaginations in the sarcolemma and extend into the interior of the cell at right angles to the contractile elements and sarcoplasmic reticulum. They transmit action potential from the sarcolemma to sarcoplasmic reticulum to release calcium causing muscle contraction.  Muscle contraction It does not necessarily mean muscle shortening because muscle tension can be produced without changes in muscle length such as holding a heavy book. Muscle contractions can be classified based on length and tension. A muscle contraction is described as isometric if the muscle tension changes but the muscle length remains the same. In contrast, a muscle contraction is isotonic if muscle tension remains the same throughout the contraction. If the muscle length shortens, the contraction is concentric; if the muscle length lengthens, the contraction is eccentric.  Types of muscle contraction Isotonic contraction Isometric contraction Item concentric eccentric Length shortening lengthening constant Tension constant constant increase Work mobilizing mobilizing stabilizing Load and Less than More than Equal or more than power power the power the power Example loading Unloading muscles of hand and forearm grip an object  Changes during muscle contraction The changes which occur during muscle contraction include: a-Electrical changes. b-Mechanical changes. c- Metabolic or Chemical changes. d-Thermal changes. e-Excitability Changes  Electrical changes Membrane potential:is the potential difference between inside and outside the cell due to the presence of very minute excess of negative charge ions inside the cell and equal number of positive ions outside the cell. Causes: Electrogenic membrane potential (pump). Diffusion membrane potential (Diffusion).  Resting membrane potential Extracellular fluid +++++++++++++++++ Na+ - -- - - - - - - - - - - - Organic compounds Intracellular fluid K+ Chemical Composition: Extracellular fluid Intracellular fluid Sodium ions (+) 143 units Potassium ions(+) 157units Potassium ions(+) 5 units Sodium ions (+) 14 units Chloride ions (-)17 units Phosphate ions (-) 113 units Bicarbonate (-)27 units Protein bases (-) 72 units Electrogenic membrane potential (pump): The sodium pump transport 3 positive charged Na+ to outside and 2 positive charged K+ to inside by 1 ATP molecule. Diffusion membrane potential (Diffusion): The negatively charged organic molecules (cellular proteins and phosphates of ATP) cannot leave the cells. The negatively charged ions attract the positively charged ions. The resting membrane is more permeable to K+ than Na+ Attraction of K+ occurs.  Action potential It is sharp sudden changes in the membrane potential by which the informational signals are transmitted from one part to another. Causes: any factor which increase the permeability of the membrane to Na+ such as: Electrical, Mechanical, chemical and thermal stimuli. Stages of action potential: Depolarization: inflow of Na+ Repolarization: outflow of K+  Skeletal muscles are stimulated by motor neurons of the somatic nervous system. Each skeletal muscle fiber is supplied with one motor nerve ending located near the middle of the fiber. Each axonal branch forms a neuromuscular junction with a single muscular fiber.  Neuromuscular junction Neuromuscular junction is formed of: 1- Motor nerve endings: have small membranous sacs (synaptic vesicles)that contain the ACH 2- Motor end plate: is a specific part of the sarcolemma that contain ACH receptors. 3- Synaptic cleft: contain ACH esterase for destruction of ACH. Neuromuscular junction Excitation – contraction coupling: It is the link between the electrical and mechanical changes during muscle contraction It includes: 1- Excitation -calcium coupling. 2-Calcium – contraction coupling. Excitation -calcium coupling: The central nervous system initiates an action potential that travels down the spinal cord to the motor neuron. Activation of motor neuron at neuromuscular junction. Depolarization of the motor nerve ending (Na+ influx). Opening of Voltage- gated calcium channel. Inflow of Ca2+ to motor nerve ending.  Fusion of axonal vesicles with the axonal membrane. Release of acetylcholine (Ach)via exocytosis. Ach diffuse across the synaptic cleft. Ach acts on receptors in the sarcolemma at the motor end plate. Changes in membrane permeability and inflow of Na+.  An action potential is generated and propagated all over the sarcolemma of the muscle fiber. The action potential travels along T tubules into the muscle fiber. Release of Ca2+ from sarcoplasmic reticulum. Calcium- contraction coupling: Calcium is released into the sarcoplasm and diffuse into the myofibrils. Calcium initiates the linking of actin and myosin filaments together. Actin sliding toward the center of each sarcomere. Shortens the sarcomere, myofibrils, muscle fibers causing contraction of the muscle.  Mechanical changes (Sliding filament theory) The contraction of a muscle occurs as the thin filament slide on the thick filament. During contraction, the sarcoplasm shortens and the thin and thick filaments overlap.  Molecular participants The sliding filament theory involves the activity of: Myosin Actin Tropomyosin Troponin ATP Calcium ions  Single cross bridge cycle Skeletal muscle contraction consists of multiple cross bridge cycle. The single cross bridge cycle consists of: Step I: Exposure of actin binding site Step II: Binding of myosin and actin. Step III: Power stroke of the cross bridge.  Step IV: Disconnecting the cross bridge Step V: Reenergizing and repositioning of the cross bridge. Step VI: Removal of calcium ions. Step I: Exposure of actin binding site: The action potential causes release of Ca2+ from SR. Binding of Ca2+ to troponin (TN-C) Conformational changes in the tropomyosin- troponin complex. Inhibition of TN-I with disconnection from actin. The modified tropomyosin uncovers the active ATP sites on G-actin molecules. Exposure of actin binding sites. Step II: Binding of myosin and actin: Binding of the energized cross bridge of myosin molecule to the actin binding site. Step III: Power stroke of the cross bridge: The binding of actin and myosin causes conformational changes of cross bridge resulting in the release of ADP and Pi At the same time, the cross bridge flexes, pulling the thin filament to the center of sarcomere. This movement is called power stroke (Back and forth movement). The chemical energy of ATP is transformed into mechanical energy of contraction (Engine). Step IV: Disconnecting the cross bridge: ATP molecule binds to its site on myosin cross bridge. Disconnect the cross bridge from the actin Muscle contraction will continue as long as there is an excess of Ca2+ ions in the sarcoplasm. Step V: Reenergizing and repositioning of the cross bridge: The release of the myosin cross bridge from the actin. Hydrolysis of ATP into ADP and Pi. Energy is transformed from the ATP to the myosin cross bridge which returns to its high energy conformation. Step VI: Removal of calcium ions: Calcium is actively transported from the cytosol to the sarcoplasmic reticulum by Ca2+ ATP pump. Troponin-Tropomyosin complex again cover the binding sites on actin.  Summary of the Steps of a Muscle Contraction 1. An action potential travels along an axon membrane to a neuromuscular junction. 2. ACh is released from the synaptic vesicles in the presynaptic terminal of the neuron by exocytosis. 3. ACh diffuses across the synaptic cleft and binds ACh receptors located on the motor endplates of the sarcolemma, and stimulates the opening of sodium channels which stimulates an action potential. 4. The action potential travels along the sarcolemma and into the T tubules which carry the wave of depolarization into the muscle cell. 5. The action potentials of the T tubules stimulate the release of calcium from the sarcoplasmic reticulum. 6. Calcium released into the sarcoplasm binds to troponin molecules, causing a change in its structure that results in the attached tropomyosin to shift position on the actin filament, which exposes attachment sites for the myosin head. 7. The myosin head (cross-bridges), previously activated by the hydrolysis of ATP to ADP and P, attaches to actin. 8. Once attached to actin, the myosin head undergoes a power stroke and pulls the thin filaments over the thick filament. The ADP and P molecules are released 9. Fresh ATP binds to the myosin head and energizes the myosin head allowing the cross-bridge to detach from actin. The myosin head bends back to its resting position and will repeat the contraction cycle an long as calcium remains attached to troponin. 10. When action potentials stop being produced, the sarcoplasmic reticulum actively retrieve calcium and tropomyosin moves over the myosin binding site on the actin filament preventing attachment of the myosin cross bridge.  Muscle relaxation Muscle relaxation requires ATP (energy source)for: 1- detachment of the myosin head from the actin filament. 2- pump Ca2+ ions back into the sarcoplasmic reticulum after contraction. 3- recovery of the membrane potential after depolarization.  Metabolic or Chemical changes The energy for contraction is derived from hydrolysis of ATP to ADP ADP is phosphorylated by Creatinephosphat (CrP) into ATP and Creatin(Cr). Cr is phosphorylated by the energy derived from food. The food energy sources in the body includes: Muscle glycogen. Blood glucose. Fats(Adipose tissue) Proteins(Amino Acids)  Energy systems ATP is the immediate source of energy for muscle contraction. The breakdown of phosphate bond of ATP release maximum energy. ATP is produced by more than one system either anaerobic or aerobic: ❑ ATP-CrP system. ❑ Anaerobic glycolysis system. ❑ Aerobic glycolytic system. ❑ Aerobic lipolytic system. ATP-CrP system: Forms a reservoir of high energy phosphate in the muscle. Cannot be used as a direct source of energy. Used for regeneration of ATP from ADP. ATP ADP + Pi + H+ CrP + ADP + H+ ATP + Cr Anaerobic glycolysis system: Glycolysis converts glucose to pyruvate, water and NADH, producing two molecules of ATP. Excess pyruvate is converted to lactic acid which causes muscle fatigue. Glucose 2ATP + 2 lactate + 2 H+ Aerobic glycolytic system: Carbohydrates + O2 38 ATP + CO2 + H2O Aerobic lipolytic system: Fats + O2 138- 456 ATP + by- products  Thermal changes The energy produced from chemical changes are used for: Mechanical work Heat (75%) (25%) for contraction and relaxation Initial Heat (45%) Recovery Heat (55%) Contraction Relaxation heat heat (30%) (15%) Initial heat (45%): Contraction heat: It is the heat produced during contraction. Relaxation heat: It is the heat produced during relaxation. It is produced during the breakdown of high energy phosphate compounds (ATP and CrP) mainly during the anaerobic phases of chemical changes. Recovery or delay heat (55%): It is greater than initial heat and is liberated for many minutes after contraction also it appears after relaxation. It is due to mainly glycolysis and oxidation of lactic acid.  Excitability changes Excitability changes are the ability of the skeletal muscle to respond to maximal stimulus. Phases of excitability curve: Absolute refractory period (ARP). Relative refractory period(RRP). Supranormal state of excitability. Subnormal state of excitability. L.P  Factors affecting simple Muscle twitch 1-Type of muscle fiber. 2-Initial length of muscle. 3-Temperature. 4-staircase phenomena.  paramters Type I fiber Type II fiber Colour Red due to: White or pale due to: High myoglobin Little myoglobin High cytochrome Low cytochrome Low Hb content High Hb content Poor in blood supply Rich in blood supply Mitochondria Many Few Metabolic energy Aerobic oxidation with Anaerobic oxidation with fast slow and continuous and sudden release of ATP release of ATP Fatigue Not easily easily  paramters Type I fiber Type II fiber Contraction: Speed Slow Fast Duration Long Short Loads Heavy Light Distance Short contraction Lengthy contraction Performance Prolonged, continuous Rapid, sudden powerful contraction contraction Example Extensors Flexors (Gluteal, Thigh) (Eye muscles)  Temperature Since a muscle contraction is a series of biochemical changes that requires enzymes so the warming of the muscle accelerates simple muscle twitch. Also warming decrease the viscosity of the muscle and facilitates the process of contraction so the height of contraction increase and the duration decrease (due to strength).  Fatigue Decrease the strength of contraction and prolong its duration and relaxation may become incomplete (due to reduction of energy source).  Staircase phenomena When muscle is repeatedly stimulated with successive stimuli at a rate which doesn’t produce fatigue the first new contraction become progressively stronger due to:  Reduced K+ ion inside the fiber and slight increase extracellular. Increase Ca2+ conc. inside the muscle results in greater contraction. Also the first contraction produce heat which warm the muscle.  Depolarization Repolarization Absolute relative Supra Sub normal normal refractory refractory State of -ve after state of period period excitabi excitabi potential lity lity +ve after potential  It is the period during which the excitability is completely lost and the muscle doesnot respond to any stimulus whatever its strength. It corresponds to: Contraction curve: L.P. Beginning of contraction. Action potential curve: Depolarization.  It is the period during which the excitability is gradually increased (0-100%) and strong stimulus is required to excite the muscle. It corresponds to: Contraction curve: The remaining part of contraction. Small part of relaxation. Action potential curve: Repolarization.  It is the period during which the excitability is more than 100% and the muscle respond by higher contraction. It corresponds to: Contraction curve: Part of relaxation. Action potential curve: Negative after potential.  It is the period during which the excitability is less than 100%. It corresponds to: Contraction curve: The end of relaxation. Action potential curve: Positive after potential.