Muscular System Lecture 1 & 2 PDF

MEDI101 / HSF-1 Muscular System: Lecture 1 & 2 Hassaan A. Rathore, PhD Associate Professor College of Pharmacy Where are we as per syllabus?  Expected learning outcomes At the end of the lecture the student should be able to: List major characteristics & fu...

MEDI101 / HSF-1 Muscular System: Lecture 1 & 2 Hassaan A. Rathore, PhD Associate Professor College of Pharmacy Where are we as per syllabus?  Expected learning outcomes At the end of the lecture the student should be able to: List major characteristics & functions of the muscular system Define and explain the role of endomysium, perimysium, epimysium. Describe sliding filament model of muscle contraction Explain neuromuscular junction Distinguish graded responses of muscle contraction  Muscle Name comes from a Latin word “musculus” meaning “little mouse” Forms the main tissue in the heart and walls of hollow organs Makes up nearly half the body’s mass  Muscle Similarities and some terminologies Skeletal and smooth muscle cells are elongated and are called muscle fibers Muscle contraction depends on two kinds of myofilaments – actin and myosin Muscle terminology is similar Sarcolemma – muscle plasma membrane Sarcoplasm – cytoplasm of a muscle cell Prefixes – myo, mys, and sarco all refer to muscle  Muscle overview The three types of muscle tissue are: Skeletal Cardiac and Smooth muscle. These types differ in structure, location, function, and means of activation Functions of muscles Movement Skeletal muscle - attached to skeleton Moves body by moving the bones / locomotion Smooth muscle – squeezes fluids and other substances through hollow organs like veins and those of the digestive system & maintains BP. Cardiac muscle – to propel blood through the body. Maintenance of body posture and position – enables the body to remain sitting or standing Joint stabilization – ex. muscle tendons around shoulder Heat generation – muscle contractions produce heat - Helps maintain normal body temperature  Functional characteristics of muscle tissue Excitability or irritability – the ability to receive and respond to stimuli Contractility – the ability to shorten forcibly Extensibility – the ability to be stretched or extended Elasticity – the ability to recoil and resume the original resting length Types of muscles Skeletal muscle tissue – packaged into skeletal muscles Makes up 40% of body weight Cells are striated and multi-nucleated (periphery); voluntary Cardiac muscle tissue – occurs only in the walls of the heart Cells are striated, uni-nucleated and branching with intercalated discs; involuntary Smooth muscle tissue – occupies the walls of hollow organs Cells lack striations (non-striated) and uni-nucleated; involuntary Open this in your browser: www.pollev.com/hassaan Table 6.1 Comparison of Skeletal, Cardiac, and Smooth Muscles Characteristic Skeletal Cardiac Smooth Body location Attached to bones or, for Walls of the heart Mostly in walls of hollow some facial muscles, to skin visceral organs (other than the heart) Cell shape and Single, very long, cylindrical, Branching chains of cells; Single, fusiform, appearance multinucleate cells with very uninucleate, striations; uninucleate; no striations obvious striations intercalated discs Connective tissue Epimysium, perimysium, and Endomysium attached to the Endomysium components endomysium fibrous skeleton of the heart Endomysium Epimysium Endomysium Endomysium Perimysium Cells Regulation of Voluntary; via nervous system Involuntary; the heart has Involuntary; nervous contraction controls a pacemaker; also nervous system controls; hormones, system controls; hormones chemicals, stretch Speed of Slow to fast Slow Very slow contraction  Basic features of skeletal muscles Muscle attachments Most skeletal muscles run from one bone to another One bone will move – other bone remains fixed Origin – less movable attachment Insertion – more movable attachment Muscles attach to origins and insertions by connective tissue Fleshy attachments – connective tissue fibers are short Indirect attachments – connective tissue forms a tendon. Bone markings present where tendons meet bones Tubercles, trochanters, tuberosity and crests  Functions of skeletal muscles Functions of skeletal muscle include  Force production for locomotion and breathing (diaphragm). Force production for postural support. Heat production during cold stress. Skeletal muscle: muscle fiber & connective tissue  Skeletal muscle micro-anatomy Each muscle is a discrete organ composed of muscle tissue, blood vessels, nerve fibers and connective tissue. The three connective tissue sheaths are: Endomysium – fine sheath of connective tissue composed of reticular fibers surrounding each muscle fiber Perimysium – fibrous connective tissue that surrounds groups of muscle fibers called fascicles Epimysium – an overcoat of dense connective tissue that surrounds the entire muscle Skeletal muscle: muscle fiber & connective tissue  Microscopic structures of skeletal muscle fibers Each fiber (cell) is a long, cylindrical cell with multiple nuclei just beneath the sarcolemma. Fibers (cells) are 10 to 100 µm in diameter, and up to several centimeters long. Each cell is a syncytium (produced by fusion of embryonic cells). Sarcoplasm has numerous glycosomes and a unique oxygen-binding protein called myoglobin. Fibers contain the usual organelles, myofibrils, sarcoplasmic reticulum, and T tubules.  Myofibrils Myofibrils are densely packed, rod-like contractile elements They make up most of the muscle volume The arrangement of myofibrils within a fiber is such that a perfectly aligned repeating series of dark A bands and light I bands is evident  Sarcomere The smallest contractile unit of a muscle fiber (cell). The region of a myofibril between two successive Z discs Composed of myofilaments made up of contractile proteins Myofilaments are of two types – thick and thin SARCOMERE  Myofibrils- Banding pattern Thick filaments – extend the entire length of an A band. Thin filaments – extend across the I band and partway into the A band. Z-disc – coin-shaped sheet of proteins (connectins) that anchors the thin filaments and connects myofibrils to one another. Thin filaments do not overlap thick filaments in the lighter H zone. M lines appear darker due to the presence of the protein desmin. Banding pattern Why are we trying to understand all this?  Ultra structure of myofilaments-Thick filaments Thick filaments are composed of the protein myosin Each myosin molecule has a rod-like tail and two globular heads Tails – two interwoven, heavy polypeptide chains Heads – two smaller, light polypeptide chains called cross bridges Ultra structure of myofilaments-Thick filaments  Ultra structure of myofilaments-Thin filaments Thin filaments are chiefly composed of the protein actin. Each actin molecule is a helical polymer of globular subunits called G-actin. The subunits contain the active sites to which myosin heads attach during contraction. Tropomyosin and troponin are regulatory subunits bound to actin. Ultra structure of myofilaments-Thin filaments Arrangement of filaments in sarcomere  Sarcoplasmic reticulum SR is an elaborate, smooth endoplasmic reticulum that mostly runs longitudinally and surrounds each myofibril Paired terminal cisternae form perpendicular cross channels Functions in the regulation of intracellular calcium levels Elongated tubes called T tubules penetrate into the cell’s interior at each A band–I band junction T tubules associate with the paired terminal cisternae to form triads Sarcoplasmic reticulum & T tubules  T tubules T tubules are continuous with the sarcolemma. They conduct impulses to the deepest regions of the muscle. These impulses signal for the release of Ca2+ from adjacent terminal cisternae. T tubules and SR provide tightly linked signals for muscle contraction. T tubule proteins act as voltage sensors. SR foot proteins are receptors that regulate Ca2+ release from the SR cisternae.  Sliding filament model Thin filaments slide past the thick ones so that the actin and myosin filaments overlap to a greater degree. In the relaxed state, thin and thick filaments overlap only slightly. Upon stimulation, myosin heads bind to actin and sliding begins. Each myosin head binds and detaches several times during contraction, to generate tension and propel the thin filaments to the center of the sarcomere. As this event occurs throughout the sarcomeres, the muscle shortens.  Sequential events of contraction Cross bridge formation – myosin cross bridge attaches to actin filament Working (power) stroke – myosin head pivots and pulls actin filament toward M line Cross bridge detachment – ATP attaches to myosin head and the cross bridge detaches “Cocking” of the myosin head – energy from hydrolysis of ATP cocks the myosin head into the high-energy state  Myosin head (high-energy configuration) 1 Myosin cross bridge attaches to the actin myofilament Thin filament ADP and Pi (inorganic Thick phosphate) released filament 4 As ATP is split into ADP and Pi, 2 Working stroke—the myosin head pivots and bends cocking of the myosin head occurs as it pulls on the actin filament, sliding it toward the M line Myosin head (low-energy configuration) 3 As new ATP attaches to the myosin head, the cross bridge detaches  Excitation contraction coupling It is the communication between the electrical events and the mechanical events that happen as a response Once generated, the action potential: Is propagated along the sarcolemma Travels down the T tubules Triggers Ca2+ release from terminal cisternae Ca2+ binds to troponin and causes: The blocking action of tropomyosin to cease Actin active binding sites to be exposed  Excitation contraction coupling Myosin cross bridges alternately attach and detach Thin filaments move toward the center of the sarcomere Hydrolysis of ATP powers this cycling process Ca2+ is removed into the SR, tropomyosin blockage is restored, and the muscle fiber relaxes Neuromuscular junction All of the events leading to muscular contraction start once a stimulus by a nerve terminal causes the generation of action potential in the sarcolemma. This action potential is then passed to all skeletal muscle fibers (myofibrils) via T-tubules causing Ca+2 to be released from sarcoplasmic reticulum and binding of actin-myosin causing contraction. Neuromuscular junction The neuromuscular junction is a junction between the motor nerve and skeletal muscle fiber.  Nerve Synaptic Cleft Sarcolemma  Neuromuscular transmission in nerve terminal When a nerve impulse reaches the end of an axon at the neuromuscular junction: Voltage-regulated calcium channels open and allow Ca2+ to enter the axon. Ca2+ inside the axon terminal causes axonal vesicles to fuse with the axonal membrane. Release of Ach from nerve terminal This fusion releases acetylcholine (Ach) into the synaptic cleft via exocytosis. ACh diffuses across the synaptic cleft to ACh receptors on the sarcolemma. Binding of ACh to its receptors initiates an action potential in the muscle.  Role of acetylcholine at nerve terminal ACh binds its receptors at the motor end plate (on sarcolemma) Binding opens chemically (ligand) gated channels Na+ diffuses inwards and the interior of the sarcolemma becomes less negative This event is called depolarization. Neuromuscular Junction  Depolarization spread Initially, this is a local electrical event called end plate potential Later, it starts an action potential that spreads in all directions across the sarcolemma Summary of events that take place in the neuromuscular junction Inside the nerve In the Space between nerve & muscle cell In the muscle cell Graded responses Summary & Questions [email protected]