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SKELETAL MUSCLE PHYSIOLOGY Pawlose Ketema Special Characteristics of Muscle Tissue • Excitability • Contractility • Extensibility • Elasticity Physiology of Skeletal Muscle Fibers • For skeletal muscle to contract • Activation (at neuromuscular junction) • Excitation-contraction coupling Nerve Stimulus of Skeletal Muscle Stimulated by motor neurons of the somatic nervous system Axons of the motor neurons travel to muscle cells (branch profusely as they enter muscles) Each branch forms a neuromuscular junction with a single muscle fiber Formation of the Neuromuscular Junction The neuromuscular junction is formed by the following components: Axonal endings containing small synaptic vesicles that contain acetylcholine (ACh) The motor end plate of a muscle, which is a specific part of the sarcolemma that contains ACh receptors Though the axonal ending and the motor end plate appear close, they are separated by a space called the synaptic cleft Neuromuscular Junction Events at Neuromuscular Junction Events at Neuromuscular Junction Destruction of ACh ACh bound to ACh receptors is quickly destroyed by the enzyme acetylcholinesterase This destruction prevents continued muscle fiber contraction in the absence of additional stimuli Breaks ACh into acetate and choline Acetate and Choline is transported back into axon terminal and used to make more ACh. Fate of Neurotransmitters • Post synaptic binding • Reuptake • Systemic circulation Myasthenia Gravis Chronic autoimmune neuromuscular disorder that is characterized by weakness of voluntary muscle groups Cause: that block ACh receptors inhibiting the excitatory effects of the ACh at nicotinic receptors Genetic in neuromuscular junction Antibodies Treatment: ACh inhibitors (make a correction it should be ACHE) Therapeutic Significance • Pharmacologic Target • • • • • Synthesis Storage Release Termination of action Receptor effect Generation and Propagation of AP in Skeletal Muscle Binding of ACh to ACh receptors opens ligand gated channels Na+ influx and K+ efflux. Na+ driving force > K+ force Change in membrane potential interior sarcolemma becomes less negative depolarization (end plate potential) Generation and Propagation of AP in Skeletal Muscle End plate potential ignites an AP spreading to adjacent membrane areas opening voltage-gated Na+ channels Once threshold is reached an AP is generated AP propagates in all directions opening more Na+ channels Generation and Propagation of AP in Skeletal Muscle As a consequence of changes in membrane potential, repolarization occurs. Na+ channels close and K+ channels open K+ diffuses out of the cells Cell is in a refractory period cell cannot be stimulated until repolarization is complete AP is unstoppable results in contraction of muscle Action Potential of Skeletal Muscle Excitation-Coupling Contraction Excitation-Coupling Contraction Rigor Mortis Recognizable sign on death After death cease in respiration deplete oxygen that is used to make ATP ATP is used to separate the cross-bridges during relaxation In rigor mortis, the myosin head remains bound to the active site muscle unable to relax Eventually, the muscle proteins break down after death and the cross-bridge breaks Diseases of Muscle Contraction Botulism/Botox: bacteria Clostridium botulinum (grows in improperly canned foods) produces botulinum toxin: toxin prevents release of Ach at neuromuscular junction, results in flaccid paralysis Tetanus: Clostridium tetani (grows in soil) produces tetanus toxin: toxin causes over stimulation of motor neurons, results in spastic paralysis Myasthenia gravis: autoimmune disease, causes loss of Ach receptors, muscles become nonresponsive Contraction of Skeletal Muscles The force that exerted by a contracting muscle on an object is called muscle tension. The opposing force exerted on the muscle by the weight of the object to be moved is called the load. The two types of muscle contraction are similar Isometric contraction – increasing muscle tension (muscle does not shorten during contraction) Tension develop but the muscle does not move Isotonic contraction – decreasing muscle length (muscle shortens during contraction) Tension develops and overcomes the load muscle shortening The Motor: The Nerve-Muscle Functional Unit A motor unit is a motor neuron and all the muscle fibers it supplies The number of muscle fibers per motor unit can vary from four to several hundred Muscles that control fine movements (fingers, eyes) have small motor units Large weight-bearing muscles (thighs, hips) have large motor units Muscle Twitch A muscle twitch is the response of a muscle to a single, brief threshold stimulus The three phases of a muscle twitch are: Latent period – first few milli-seconds after stimulation when excitation-contraction coupling is taking place Period of contraction- cross bridges actively form and the muscle shortens Period of relaxation- Ca2+ is reabosorbed into the SR, and muscle tension goes to zero Graded Muscle Response Graded muscle responses are: Variations in the degree of muscle contraction Required for proper control of skeletal movement Responses are graded by: Changing the frequency of stimulation Changing the strength of the stimulus Muscle Response to Varying Stimuli A single stimulus results in a single contractile response – a muscle twitch Frequently delivered stimuli (muscle does not have time to completely relax) increases contractile force – wave summation More rapidly delivered stimuli result in incomplete tetanus If stimuli are given quickly enough, complete tetanus results Muscle Response: Stimulation Strength Sub-threshold stimuli -that produce no observable contractions Threshold stimulus – the stimulus strength at which the first observable muscle contraction occurs Maximal stimulus – the strongest stimulus that increases contractile force The point at which all the muscle’s motor units are recruited Increasing the stimulus intensity does not produce a stronger contraction Stimulus Intensity and Muscle Tension Force of contraction is precisely controlled by multiple motor unit summation This phenomenon, called recruitment, brings more and more muscle fibers into play The recruitment process is dictated by the size principle. Why is the size principle important? Isotonic Contractions In Isotonic contractions, the muscle changes length and moves the load. The two type of isotonic contractions and concentric and eccentric Concentric contractions – the muscle shortens and does work Eccentric contractions – the muscle contracts as it lengthens Isometric contractions: Tension increases to the muscle’s capacity, but the muscle neither shortens nor lengthens Occurs if the load is greater than the tension the muscle is able to develop Muscle Metabolism: Energy for Contraction ATP is the only source used directly for contractile activity Muscles store a limited amount of ATP (~4-6 seconds worth) ATP regenerated within a fraction of a second via these pathways: Direct phosphorylation Anaerobic glycolysis Aerobic respiration Direct Phosphorylation of ADP by Creatine Phosphate (CP) CP is a unique highenergy molecule stored in muscles (used during vigorous exercise) Used while body regenerates ATP while the metabolic pathways adjust to the suddenly higher demand for ATP Muscle cells store 2-3 more times CP than ATP Together CP and ATP provide maximum muscle power for 15 seconds Anaerobic Pathway: Glycolysis and Lactic Acid Formation Used when ATP and CP stores are exhausted ATP is generated by breaking down (catabolizing) glucose obtained from the blood or glycogen stored in the muscle Glycolysis Pyruvic can produce ATP depending on its environment (presence or absence of O2) Use in the presence and absence of O2 but does not use it Glucose 2 pyruvic release 2 ATP Under anaerobic conditions, lactic acid, the end product, is formed. Typically, lactic acid diffuses out of the muscles into blood stream used by liver and kidney and converted into pyruvic acid or glucose Too much lactic acid creates the burning sensation felt during exercise Aerobic Respiration Since CP is limited, the muscle must metabolize nutrients to transfer energy from foodstuff ATP Include glycolysis (continuation of anaerobic respiration) Aerobic respiration takes place in the mitochondria and requires oxygen Initial exercise – glycogen provides most of the energy 0-30 min of exercise – glucose and fatty acid are major sources of energy 30 min and above – fatty acid are the major fuel Aerobic respiration yields ~ 32 ATP per glucose but it is slow due to the many steps and the high demand for oxygen and nutrients to keep going Overview of ATP Pathways Force of Contraction The force of contraction depends on the number of myosin cross bridges that are attached. The 4 factors that affect the force of contraction: 1) 2) 3) 4) The number of muscle fibers stimulated Relative size of fibers Frequency of stimulation Degree of muscle stretch Factors that Affect the Force of Contraction The number of muscle fibers stimulated 1. The more motor units recruited, the greater the muscle force Relative size of fibers 2. The bulkier the muscle The more tension greater the strength Regular resistance exercise increases muscle force by causing the muscle to hypertrophy (increases muscle size) Factors that Affect the Force of Contraction Frequency of Stimulation 3. Rapid stimulation summation leads to stronger contraction Degree of muscle strength 4. muscles contract strongest when muscle fibers are 80-120% of their normal resting length Muscle Fiber Type: Functional Characteristics Speed of contraction – determined by speed in which ATPases split ATP The two types of fibers are slow and fast ATP-forming pathways Oxidative fibers – use aerobic pathways Glycolytic fibers – use anaerobic glycolysis These two criteria define three categories – slow oxidative fibers, fast oxidative fibers, and fast glycolytic fibers Muscle Fiber Type: Speed of Contraction Slow oxidative fibers contract slowly, have slow acting myosin ATPases, and are fatigue resistant Fast oxidative fibers contract quickly, have fast myosin ATPases, and have moderate resistance to fatigue Fast glycolytic fibers contract quickly, have fast myosin ATPases, and are easily fatigued