Muscular system.pdf

Muscular System Manipal College of Pharmaceutical Sciences  Compare and contrast skeletal, cardiac and smooth muscle. (10) Manipal College of Pharmaceutical Sciences 2 Types of Muscular Tissue Three types of muscular tissue – Skeletal – Cardiac – Smoo...

Muscular System Manipal College of Pharmaceutical Sciences  Compare and contrast skeletal, cardiac and smooth muscle. (10) Manipal College of Pharmaceutical Sciences 2 Types of Muscular Tissue Three types of muscular tissue – Skeletal – Cardiac – Smooth Manipal College of Pharmaceutical Sciences 3  Skeletal Muscle Microscopy Long, cylindrical fiber with many peripherally located nuclei Unbranched Striated Location: Attached to bones Fiber Diameter and length: Very large Manipal College of Pharmaceutical Sciences 4  Auto rhythmicity: No Nervous control- Voluntary (Somatic Nervous system) Contraction regulation: Acetylcholine released by somatic neurons Source of Calcium: Sarcoplasmic reticulum Regulator proteins for contraction: Troponin and Tropomyosin Speed of contraction: Fast Manipal College of Pharmaceutical Sciences 5  Cardiac Muscle Microscopy Branched, cylindrical fiber with one centrally located nuclei Intercalated disc Striated Location: Heart Fiber Diameter and length: Large Manipal College of Pharmaceutical Sciences 6  Auto rhythmicity: Yes Nervous control- Involuntary (Autonomic Nervous system) Contraction regulation: Acetylcholine and norepinephrine released by autonomic neurons Source of Calcium: Sarcoplasmic reticulum and interstitial fluid Regulator proteins for contraction: Troponin and Tropomyosin Speed of contraction: Moderate Manipal College of Pharmaceutical Sciences 7 Cardiac muscle contraction 1. Starts by sodium entering cell --> 2. Stimulates the release of calcium from sarcoplasmic reticulum --> 3. Calcium then binds to filaments called troponin and tropomyosin (filaments that cover actin) --> 4. Myosin is free to bind to actin (actin exposed to myosin) Manipal College of Pharmaceutical Sciences 8  Smooth Muscle Microscopy Thickest in middle, tapered at each end, central nucleus Not striated Location: Eye, Blood vessels, Airways, GIT, Ureter, Uterus Fiber Diameter and length: Small Manipal College of Pharmaceutical Sciences 9  Auto rhythmicity: Yes Nervous control- Involuntary (Autonomic Nervous system) Contraction regulation: Acetylcholine and norepinephrine released by autonomic neurons Source of Calcium: Sarcoplasmic reticulum and interstitial fluid Regulator proteins for contraction: Calmodulin and myosin light chain kinase Speed of contraction: Slow Manipal College of Pharmaceutical Sciences 10 Manipal College of Pharmaceutical Sciences 11 Skeletal Muscle Contraction Manipal College of Pharmaceutical Sciences  Describe the physiology of skeletal muscle contraction (10) With the help of a diagram explain in the structure of a muscle cell (5) Discuss the proteins associated with skeletal muscle and its functions (5) Explain the steps in the contraction cycle of a skeletal muscle (5) Manipal College of Pharmaceutical Sciences 13  Skeletal muscles are composed of clusters of muscle cells. – Muscle fibers A muscle consists of packages of muscle cells called fascicles A muscle cell is long, and spindle shaped The neurons that stimulate skeletal muscle to contract are somatic motor neurons Manipal College of Pharmaceutical Sciences 14  Cell structure – Muscles cells contain many nuclei – The plasma membrane→ sarcolemma – The cytoplasm→ sarcoplasm Myofibrils→ – elongated protein molecules – aligned in parallel arrangements – extend the full length of the cell. – Myofibril contains contractile units called sarcomeres – Z discs separate one sarcomere from next Manipal College of Pharmaceutical Sciences 15  Muscle proteins – Myofibrils are built from three kinds of proteins 1) Contractile proteins- Myosin and actin – Generate force during contraction 2) Regulatory proteins- Troponin and tropomyosin – Switch the contraction process on and off 3) Structural proteins- Titin and dystrophin – Align the thick and thin filaments properly – Provide elasticity and extensibility – Link the myofibrils to the sarcolemma Manipal College of Pharmaceutical Sciences 16 Manipal College of Pharmaceutical Sciences 17  The myofibril consists of protein chains called myofilaments – Myofilaments have a symmetrical, alternating pattern of thick and thin elements. Thick myofilament consists of a large number of bundled myosin molecules aligned in overlapping arrays. hexameric proteins with two identical heavy chains and two pairs of different light chains. – regulatory light chain (RLC) – essential light chain (ELC) Manipal College of Pharmaceutical Sciences 18  The thin myofilament (filamentous actin) – made up of two helically intertwined chains of actin (globular actin) units. Other proteins that bind to the actin molecules: Tropomyosin The Troponin complex→ made up of three members Manipal College of Pharmaceutical Sciences 19  Titin a structural protein – Titin Stabilize the position of myosin accounts for much of the elasticity and extensibility of myofibrils – Dystrophin Links thin filaments to the sarcolemma Manipal College of Pharmaceutical Sciences 20  Sliding Filament Mechanism – Myosin heads attach to and “walk” along the thin filaments at both ends of a sarcomere – Progressively pulling the thin filaments toward the center of the sarcomere – Z discs come closer together and the sarcomere shortens – Leading to shortening of the entire muscle Manipal College of Pharmaceutical Sciences 21  Contraction Cycle At the onset of contraction, SR releases calcium to cytosol They bind to troponin Troponin moves tropomyosin away from the myosin binding sites on actin Once binding sites are free the contraction cycle starts which consist of 4 steps Manipal College of Pharmaceutical Sciences 22  Contraction Cycle Step 1- ATP hydrolysis Myosin head includes an ATP binding site and an ATPase ATPase hydrolyzes ATP to ADP and phosphate group. This hydrolysis reaction reorients and energize myosin head Step 2- Attachment of myosin to actin to form cross-bridges The energized myosin head attaches to the myosin-binding site on actin and releases the phosphate group. When the myosin head attach to actin they are referred to as cross-bridges Manipal College of Pharmaceutical Sciences 23  1 Myosin heads Key hydrolyze ATP and : = Ca 2+ become reoriented AD and energized PP Contraction cycle continues if ATP is available and Ca 2+ level in the sarcoplasm is high  1 Myosin heads Key hydrolyze ATP and : = Ca 2+ become reoriented AD and energized PP 2 Myosin heads bind to actin, P forming crossbridges Contraction cycle continues if ATP is available and Ca 2+ level AD in P the sarcoplasm is high  Contraction Cycle Step 3- Power Stroke The site on the cross-bridge where ADP is bound opens. The cross-bridge rotates and releases the ADP This generate force sliding the thin filament past the thick filament Step 4- Detachment of myosin from actin As the next ATP binds to the myosin head, the myosin head detaches from actin The contraction cycle repeats as long as ATP is available and the Ca++ level is sufficiently high Continuing cycles applies the force that shortens the sarcomere Manipal College of Pharmaceutical Sciences 26  1 Myosin heads Key hydrolyze ATP and : = Ca 2+ become reoriented AD and energized PP Contraction cycle continues if ATP is available and Ca 2+ level in the sarcoplasm is high  1 Myosin heads Key hydrolyze ATP and : = Ca 2+ become reoriented AD and energized PP 2 Myosin heads bind to actin, P forming crossbridges Contraction cycle continues if ATP is available and Ca 2+ level AD in P the sarcoplasm is high  1 Myosin heads Key hydrolyze ATP and : = Ca 2+ become reoriented AD and energized PP 2 Myosin heads bind to actin, P forming crossbridges Contraction cycle continues if ATP is available and Ca 2+ level AD in P the sarcoplasm is high AD P 3 Myosin crossbridges rotate toward center of the sarcomere (power stroke)  1 Myosin heads Key hydrolyze ATP and : = Ca 2+ become reoriented AD and energized PP 2 Myosin heads bind to actin, P forming crossbridges AT Contraction cycle continues if P ATP is available and Ca 2+ level AD in P the sarcoplasm is high AT AD P P 4 As myosin heads bind ATP, the crossbridges 3 Myosin crossbridges detach rotate toward center of from actin the sarcomere (power stroke) Clinical Connection What is rigor mortis? - After death, cellular membrane becomes leaky – Calcium leak out from SR, myosin binds to actin – ATP synthesis stops – So, the cross bridges cannot detach from actin – Resulting condition, muscles are in state of rigidity (cannot contract or stretch) is called rigor mortis (rigidity of death) Rigor mortis begins 3-4 hours after death and lasts for 24hours Manipal College of Pharmaceutical Sciences 32  Neuromuscular Junction Manipal College of Pharmaceutical Sciences  Describe the structure and events in neuromuscular junction (10) Discuss the action of acetylcholine in NMJ (5) How is muscle action potential is produced? (5) Manipal College of Pharmaceutical Sciences 34  Neurons that stimulate skeletal muscle fibers to contract are called somatic motor neurons Somatic motor neurons are connected to spinal cord and brain A muscle fiber contracts in response to the action potentials propagating along its sarcolemma Manipal College of Pharmaceutical Sciences 35  Synapse- A region where communication occurs between two neurons or a neuron and a target cell A somatic motor neuron and skeletal muscle fiber A gap between two synapses – Synaptic cleft Neurons communicates with muscle by releasing a chemical called neurotransmitter Muscle action potential arise at the neuromuscular junction Synapse between somatic neuron and skeletal muscle fiber Manipal College of Pharmaceutical Sciences 36 Step 1- Release of Acetylcholine 1. Release of Acetylcholine Nerve impulse arrive at synaptic end bulbs Synaptic vesicles undergo exocytosis Liberates Acetyl choline to synaptic cleft Ach diffuses across synaptic cleft between motor neuron and motor end plate Manipal College of Pharmaceutical Sciences 37  Axon collateral of Axon terminal somatic motor neuron Nerve impulse Synaptic vesicle Sarcolemma containing Axon terminal acetylcholine Synaptic (ACh) end bulb Motor Synaptic end end bulb Neuromuscular plate junction (NMJ) Synaptic cleft Sarcolemma (space) Myofibril (b) Enlarged view of the neuromuscular junction (a) Neuromuscular junction 1 1ACh is released Synaptic end bulb from synaptic vesicle Synaptic cleft (space) Motor end plate Junctional fold (c) Binding of acetylcholine to ACh receptors in the motor end plate Step 2- Activation of Acetylcholine receptors Ach binds to receptors of acetylcholine in motor end plate Ion channels in the Ach receptor open Once channel is open, sodium flow across the membrane Manipal College of Pharmaceutical Sciences 39  Axon collateral of Axon terminal somatic motor neuron Nerve impulse Synaptic vesicle Sarcolemma containing Axon terminal acetylcholine Synaptic (ACh) end bulb Motor Synaptic end end bulb Neuromuscular plate junction (NMJ) Synaptic cleft Sarcolemma (space) Myofibril (b) Enlarged view of the neuromuscular junction (a) Neuromuscular junction 1 1ACh is released Synaptic end bulb from synaptic vesicle Synaptic cleft (space) Motor end plate 2 2 ACh binds to Ach receptor Na+ Junctional fold (c) Binding of acetylcholine to ACh receptors in the motor end plate  Step 3- Production of muscle action potential Inflow of sodium makes the inside of muscle fiber more positively charged This change in membrane potential triggers muscle action potential Once channel is open, sodium flow across the membrane Muscle AP propagates along the sarcolemma in to T tubule system This causes SR to release stored calcium in to sarcoplasm and muscle contracts Manipal College of Pharmaceutical Sciences 41  Axon collateral of Axon terminal somatic motor neuron Nerve impulse Synaptic vesicle Sarcolemma containing Axon terminal acetylcholine Synaptic (ACh) end bulb Motor Synaptic end end bulb Neuromuscular plate junction (NMJ) Synaptic cleft Sarcolemma (space) Myofibril (b) Enlarged view of the neuromuscular junction (a) Neuromuscular junction 1 1ACh is released Synaptic end bulb from synaptic vesicle Synaptic cleft (space) Motor end plate 2 2 ACh binds to Ach receptor Na+ Junctional fold 3 Muscle action potential is produced (c) Binding of acetylcholine to ACh receptors in the motor end plate Step 4- Termination of Acetylcholine activity Effect of Acetylcholine lasts only brief Acetylcholine is broken down by an enzyme called acetylcholinesterase Acetyl cholinesterase breaks down acetylcholine into acetyl and choline Cannot activate acetyl choline receptors Manipal College of Pharmaceutical Sciences 43  Axon collateral of Axon terminal somatic motor neuron Nerve impulse Synaptic vesicle Sarcolemma containing Axon terminal acetylcholine Synaptic (ACh) end bulb Motor Synaptic end end bulb Neuromuscular plate junction (NMJ) Synaptic cleft Sarcolemma (space) Myofibril (b) Enlarged view of the neuromuscular junction (a) Neuromuscular junction 1 1ACh is released Synaptic end bulb from synaptic vesicle Synaptic cleft (space) 4 ACh is broken down Motor end plate 2 2 ACh binds to Ach receptor Na+ Junctional fold 3 Muscle action potential is produced (c) Binding of acetylcholine to ACh receptors in the motor end plate  Axon collateral of Axon terminal somatic motor neuron Nerve impulse Synaptic vesicle Sarcolemma containing Axon terminal acetylcholine Synaptic (ACh) end bulb Motor Synaptic end end bulb Neuromuscular plate junction (NMJ) Synaptic cleft Sarcolemma (space) Myofibril (b) Enlarged view of the neuromuscular junction (a) Neuromuscular junction 1 1ACh is released Synaptic end bulb from synaptic vesicle Synaptic cleft (space) Motor end plate Junctional fold (c) Binding of acetylcholine to ACh receptors in the motor end plate  Axon collateral of Axon terminal somatic motor neuron Nerve impulse Synaptic vesicle Sarcolemma containing Axon terminal acetylcholine Synaptic (ACh) end bulb Motor Synaptic end end bulb Neuromuscular plate junction (NMJ) Synaptic cleft Sarcolemma (space) Myofibril (b) Enlarged view of the neuromuscular junction (a) Neuromuscular junction 1 1ACh is released Synaptic end bulb from synaptic vesicle Synaptic cleft (space) Motor end plate 2 2 ACh binds to Ach receptor Na+ Junctional fold (c) Binding of acetylcholine to ACh receptors in the motor end plate  Axon collateral of Axon terminal somatic motor neuron Nerve impulse Synaptic vesicle Sarcolemma containing Axon terminal acetylcholine Synaptic (ACh) end bulb Motor Synaptic end end bulb Neuromuscular plate junction (NMJ) Synaptic cleft Sarcolemma (space) Myofibril (b) Enlarged view of the neuromuscular junction (a) Neuromuscular junction 1 1ACh is released Synaptic end bulb from synaptic vesicle Synaptic cleft (space) Motor end plate 2 2 ACh binds to Ach receptor Na+ Junctional fold 3 Muscle action potential is produced (c) Binding of acetylcholine to ACh receptors in the motor end plate  Axon collateral of Axon terminal somatic motor neuron Nerve impulse Synaptic vesicle Sarcolemma containing Axon terminal acetylcholine Synaptic (ACh) end bulb Motor Synaptic end end bulb Neuromuscular plate junction (NMJ) Synaptic cleft Sarcolemma (space) Myofibril (b) Enlarged view of the neuromuscular junction (a) Neuromuscular junction 1 1ACh is released Synaptic end bulb from synaptic vesicle Synaptic cleft (space) 4 ACh is broken down Motor end plate 2 2 ACh binds to Ach receptor Na+ Junctional fold 3 Muscle action potential is produced (c) Binding of acetylcholine to ACh receptors in the motor end plate