Skeletal Muscle Contraction Mechanism PDF

Muscle Physiology Shirley Mwaanga  Learning goals Muscle contractile responses of the skeletal muscle Muscle contractile responses of the smooth muscle Muscle contractile responses of the cardiac muscle Mechanism of contraction in skeletal muscle  Mu...

Muscle Physiology Shirley Mwaanga  Learning goals Muscle contractile responses of the skeletal muscle Muscle contractile responses of the smooth muscle Muscle contractile responses of the cardiac muscle Mechanism of contraction in skeletal muscle  Muscle Contractile Responses The term "excitation-contraction coupling" refers to the mechanism by which the action potential causes the myofibrils of the muscle cell/fibre to contract  Skeletal Muscle Each muscle fibre behaves as a single unit, is multinucleated, and contains myofibrils Myofibrils are surrounded by the sarcolemma which form deep invaginations called transverse tubules (T tubules) within myofibril Each myofibril contains interdigitating thick and thin filaments, which are arranged longitudinally and cross- sectionally in sarcomeres  Structure of skeletal muscle: Microstructure Sarcolemma Further divisions of Plasma membrane of the myofibrils muscle fibre Z-line A-band Myofibrils I-band Threadlike strands within muscle fibres Actin (thin filament) has: Sarcoplasm Troponin Sarcoplasmic reticulum Tropomyosin Storage sites for calcium Surrounds myofibrils Myosin (thick filaments) Transverse tubules  Structure of skeletal muscle: Microstructure Divisions of myofibrils  Skeletal muscle It is the interaction between the heads of the cross bridges and the actin filaments that causes contraction  Sequence of steps leading to muscle contraction The following sequential steps: An action potential travels along a motor nerve to its terminal end At each terminal end, the nerve secretes a small amount of the neurotransmitter acetylcholine (ACh) ACh acts on a local area of the muscle fibre membrane to open multiple “ACh-gated" cation channels on the muscle fibre membrane  Sequence of steps leading to muscle contraction Opening of ACh-gated ion channels allows large quantities of Na⁺ ions to flow into the interior of the muscle fibre This causes a local depolarization that in turn leads to opening of voltage-gated Na⁺ channels. This initiates an action potential (AP) at the local area of the muscle fibre membrane The AP spreads throughout the fibre and especially within the T-tubules, deep inside the muscle fibre  How does depolarisation in the T-tubule membrane open Ca²⁺ Channels on sarcoplasmic reticulum (SR) membrane? Located in the T-tubule, closely associated with the foot of the sarcoplasmic reticulum, is a Ca²⁺ ion channel voltage sensor, dihydropyridine receptor (DHPR) The impulse passes to the L-tubules containing another receptor – Ryanodine receptor (RyR), located in the membranes of SR terminal cisternae The impulse causes RyRs to open and release Ca²⁺ into the intracellular of the muscle fibre Excitation-Contraction Coupling of skeletal muscle  The contraction sequence that follow: The free Ca²⁺ binds to troponin C protein, component on the actin filaments The troponin complex; is made of troponin T, troponin I, troponin C; then undergoes a conformational change that moves the tropomyosin molecule This action uncovers the myosin-binding sites  The contraction sequence that follow: Myosin head binds to the actin filament. The release of ADP+iP are tightly coupled to the power stroke, thus resulting in shortening of sarcomere Figure 6-8 The walk-along mechanism for contraction of the muscle  The Sliding Filament Theory Most widely accepted theory. It explains how muscle fibres contract According to this theory, myosin filaments use energy from ATP to 'walk' along the actin filaments with their cross bridges. This pulls the actin filaments closer together  Relaxation of the muscle fibre after contraction After the power stroke, ATP binds to myosin head (ATP hydrolysis occurs), this releases myosin from actin, and that changes the cross-bridge to its detached state Relaxation occurs when Ca²⁺ ions is reaccumulated in the sarcoplasmic reticulum by the Sarcoendoplasmic Reticulum Ca²⁺ ATPase (SERCA( pump, following musclecontraction  Rigor Mortis Several hours after death, all the muscles of the body go into a state of contracture called "rigor mortis"; the muscles contract and become rigid, even without action potentials This rigidity results from loss of all the ATP; required to cause separation of the cross-bridges from the actin filaments during the relaxation process The muscles remain in rigor until the muscle proteins deteriorate about 15 to 25 hours later, which presumably results from autolysis caused by enzymes released from lysosomes All these events occur more rapidly at higher temperatures Characteristics of whole muscle contraction  Length-Tension Relationship Amount of tension generated depends on length of muscle before it is stimulated – Length-tension relationship – Overly contracted (weak contracted results) Thick filaments too close to z discs and can't slide – Too stretched (weak contraction results) – Little overlap of thin and thick does not allow many cross bridges to form – Optimal resting length produces greatest force when muscle contracts Muscle tone – is the continuous and passive partial contraction of muscles, during resting state Effect of muscle length on force of contraction - whole intact muscle Active tension decreases as the muscle is stretched beyond its normal length  The relationship of contraction velocity to the load When the load has been increased to equal the maximum force that the muscle can exert, the velocity of contraction becomes zero and no contraction results, despite activation of the muscle fibre  Types of muscle contraction Isometric versus isotonic contraction Isometric - muscle does not shorten during contraction but develops maximal tension e.g. grip isotonic - muscle shorten but tension on the muscle remains constant throughout the contraction e.g. lifting a load Note : Isotonic contractions do work (Work = force x distance) Characteristics of isometric twitches recorded from different muscles Force Summation Summation means the adding together of individual twitch contractions to increase the intensity of overall muscle contraction Can occurs in two ways: Multiple fibre summation (increase in No. of motor unit contractions) Frequency summation (increasing the frequency of contractions) Motor unit – all muscle fibres innervated by a single nerve fibre  MECHANISM OF TETANUS If the muscle is stimulated repeatedly, there is insufficient time for the SR to reaccumulate Ca⁺² and the intracellular Ca⁺² concentration never returns to the low levels that exist during relaxation Instead, the level of intracellular Ca²⁺ concentration remains high, resulting in continuous binding of Ca⁺² to troponin C and continuous cross-bridge cycling. In this state, there is a sustained contraction called tetanus, rather than just a single twitch  Muscle Fatigue Prolonged and strong contraction of a muscle leads to the well- known state of muscle fatigue Studies in athletes:- muscle fatigue is directly proportion to the rate of depletion of muscle glycogen, results in: Failure of contractile and metabolic processes of the muscle fibres to continue supplying the same work output Diminished transmission of nerve signal through the neuromuscular junction after intense prolonged muscle activity Interruption of blood flow through a contracting muscle leads to almost complete muscle fatigue within 1 or 2 minutes because of the loss of nutrient supply, especially loss of O₂ Muscle fatigue diminishes muscle contraction  Read on….. Muscle contractile responses of smooth muscle  References Guyton and Halls (2021), ' Textbook of Medical Physiology - Contraction and Excitation of Skeletal, Smooth and Cardiac muscle, 14th Edition, page Chapter 7; 8; page 93; 101 Barrett K. E. (2012), Ganong's Review of Medical Physiology, 24th Edition, chapter 5