YAW BBL_WebCT Muscle Lecture_Lecture2 (1) PDF

Dr Yasser Abdel-Wahab (Module Coordinator) WEEK 2 Introduction to Anatomy and Physiology of Muscle Aims: To give an overview of the Anatomy and Physiology of Muscle Lecture Outlines: 1. Organization of the muscular system. 2. Classification and naming of skeletal muscle. 3. Function and...

Dr Yasser Abdel-Wahab (Module Coordinator) WEEK 2 Introduction to Anatomy and Physiology of Muscle Aims: To give an overview of the Anatomy and Physiology of Muscle Lecture Outlines: 1. Organization of the muscular system. 2. Classification and naming of skeletal muscle. 3. Function and characteristics of the different muscle types. 4. Functional components of skeletal muscle. 5. Action potentials in nerves and muscle. 6. Contractile proteins and muscle contraction. 7. Fast and slow muscles. 8. Skeletal muscle contraction and types of contraction. 9. Metabolism in resting and active muscle. 10. Muscle tension and control. 11. Muscle performance, fatigue and recovery. 12. Isotonic and isometric contractions 13. Integration of muscular system with other organ systems Intended Learning outcomes are:  Give an overview of the anatomy of the three main types of muscle tissue  Describe the importance of muscle movement, naming and muscle groups  Overview of skeletal muscle and naming of skeletal muscle  Describe the characteristics and functions of muscle tissue.  Give an overview of the functional components of skeletal muscle.  Identify the components of the neuromuscular junction and the differences between action potentials in nerve and muscle.  Outline the structural components of a sarcomere.  Explain the key steps in the contraction of skeletal muscle and the regulatory role of tropomyosin and troponin.  Give an overview of excitation-contraction coupling.  Appreciate the key characteristics and different types of skeletal muscle contraction.  Describe the mechanisms by which muscle fibres obtain the energy to power contractions and appreciate the factors regulating performance and fatigue.  Appreciate the integration of the muscular system with other body systems. 1  Dr Yasser Abdel-Wahab (Module Coordinator) MUSCLE TISSUE Muscle tissues refer to all contractile tissues in the body There are three types of muscle tissue:  Skeletal muscle tissue (attached to bone and responsible for movement).  Cardiac muscle tissue (heart muscle).  Smooth muscle tissue (muscle tissue around blood vessels and other organs such as intestinal tract). The main functions of muscle are: for motion; stabilizing the body position and regulating organ volumes; and thermogenesis (regulation of heat). Skeletal muscle tissue (Muscular system) Diagram of muscle fiber (muscle cell) and its constituents Skeletal muscle has an abundant nerve and blood supply, to control movement, supply oxygen and nutrients and remove metabolic waste. Microscopic anatomy of muscle Muscle fibres (muscle cells) can have diameters of up to 100 m and be up to 30 cm in length. Individual muscle fibers (muscle cells) are surrounded by a plasma membrane known as the sarcolemma. They contain intracellular fluid called sarcoplasm (like cytoplasm). They contain transverse tubules (T-tubules) which are continuous with the sarcolemma and extend into the muscle transversely surrounding all myofibrils. These T-tubules allow rapid signal transduction for contraction to occur simultaneously along the muscle. Muscle fibers contain numerous myofibrils made up of thin filaments (composed mainly of actin) and thick filaments (composed mainly of myosin) surrounded by sacroplasmic reticulum and mitochondria. These myofibrils are responsible for muscle fibre contraction. Organisation of skeletal muscle Diagram showing the organization of skeletal muscle Skeletal muscle:  Consists of fascicles (bundles of muscle fibres) enclosed by the epimysium (collagen fiber layer).  Bundles are separated by connective tissue fibres of the perimysium,  Within each bundle the muscle fibres are surrounded by the endomysium. 2  Dr Yasser Abdel-Wahab (Module Coordinator)  There are also satellite cells within the endomysium which function to repair damaged muscle. Cardiac muscle tissue Diagram showing (a) light micrograph of muscle tissue, (b) and (c) structure of Cardiac muscle cells (cardiac myocytes): a cardiac muscle cell  Contain organized myofibrils like skeletal muscle  Have aligned sacromeres giving striated appearance  Are quite small (10-20 m diameter and 50-100 m long)  Have a single central nucleus (may have more than one nucleus)  Are branched  Have short but broad T-tubules  Each cell is closely connected to other cardiac myocytes at the intercalated discs.  Action potentials in cardiac muscle can travel across these intercalated discs.  This enables the entire heart muscle to act like a single large muscle cell.  Are dependent on aerobic metabolism and contain glycogen and lipids, numerous mitochondria and excess myoglobin to store needed oxygen Smooth muscle tissue Smooth muscle can form sheets, bundles or sheaths. Many visceral organs contain several layers of smooth muscle tissue orientated in different ways. As a result, a single sectional view shows a smooth muscle cell in longitudinal and traverse section. Around blood vessels they can contract or relax to regulate blood flow. Diagram showing organization of Smooth muscle cells are: smooth muscle cells  Organized differently to skeletal and cardiac muscle  Long and thin (5-10 m diameter; 30 – 200 m long)  Spindle shaped with single central nucleus  Have no T-tubules  Lacking myofibrils and sarcomeres  Are non-striated  Thick filaments are scattered throughout sacroplasm  Have more myosin heads per thick filament than skeletal and cardiac muscle  Have thin filaments attached to dense bodies (some of which are attached to sarcolemma).  Twist like a corkscrew when contracting 3  Dr Yasser Abdel-Wahab (Module Coordinator) How skeletal muscles produce movement  Origin – tendons are attached to fixed bone  Insertion – attachment of muscle to moveable bone  Belly (gaster) – the main bulk of muscle  Lever – rigid bone which moves around fulcrum  Fulcrums – e.g is elbow joint  Primer mover and antagonist – groups of muscle acting together to cause a movement (e.g primer mover contracts while antagonist relaxes)  Synergists – help the primer mover to move about a fulcrum  Fixators – fix the positions of the joints Naming skeletal muscles The names of almost 700 skeletal muscles are based on several characteristics 1. Direction of muscle fibres – rectus abdominus runs parallel to midline 2. Location – tibiala fronterus in front of the tibia 3. Size – gluteus maximus, longus, medius 4. Number of origins – biceps (2 origins), triceps (3 origins) 5. Shape – trapezius, rhomboidus 6. Origin and insertion – sternocleidomastoid originates in sternum and inserts to the mastoid bone. 7. Action: a. Flexors b. Extensors – increase angle of wrist c. Abductors – move bone away from midline d. Levator – e.g. muscle of upper eyelid e. Depressor f. Supinator, Pronator g. Sphincter – e.g urethral sphincter of bladder control release of urine h. Tensor and Rotator Muscle Groups 4  Dr Yasser Abdel-Wahab (Module Coordinator) The diagrams below shows the names of the anterior (A) and posterior (B) superficial skeletal muscles (A) (B) The diagram below shows the names of the anterior muscle of the head and neck (A) and the muscles of facial expression (B) (A) (B) 5  Dr Yasser Abdel-Wahab (Module Coordinator) The diagram below shows the extrinsic skeletal muscles involved in eye movement Muscle Physiology Muscle tissue Specialized for contraction Has distinct properties from those of other cells. Cytoplasm is referred to as sarcoplasm Cell membrane is referred to as sarcolemma The table below shows the location and function of different types of muscle tissue 6  Dr Yasser Abdel-Wahab (Module Coordinator) The three different types of muscle have different characteristics as outlined in the table below Characteristics Skeletal muscle Cardiac muscle Smooth muscle Appearance Long, cylindrical Branched cylinder Spindle-shaped fibre Unbranched Striated No striations Striated Fibre diameter Very large Large Small (10 – 100 m) (14 m) (3-8 m) Connective tissue Epimysium Endomysium Endomysium components Perimysium Endomysium Fibre length 100 m – 30 cm 50 – 100 m 30 – 200 m Filament length Sarcomeres along Sarcomeres along Scattered throughout myofibrils myofibrils sarcoplasm 2+ Ca source Sarcoplasmic reticulum Sarcoplasmic reticulum Sarcoplasmic reticulum and ECF and ECF Speed of contraction Fast, may be tetanized Moderate, cannot be Slow, may be tetanized Rapid fatigue tetanized Fatigue resistant Fatigue resistant Nervous control Voluntary (somatic Involuntary (ANS) Involuntary (ANS) nervous system) Contraction ACh released by ACh, noradrenaline ACh, noradrenaline somatic motor neurons released by motor released by motor neurons neurons Several hormones Several hormones Local chemical changes (pH, O2 and CO2 levels) Functional components of skeletal muscle include: Motor neurons Nerve cells whose axons innervate skeletal muscle fibres. Cell bodies located in brainstem or spinal cord. Axons are myelinated. Large diameter and hence propagate action potentials at high velocities. Neuromuscular junction Site where nerve fibre and muscle fibre meet. Region of single muscle fibre membrane lying directly under terminal portion of axon specialized to form a motor end plate. Membranes of nerve fibre and muscle fibre are separated by synaptic cleft. Transmission across cleft is mainly via the neurotransmitter acetylcholine (ACh). Motor unit Comprises a motor neuron and the muscle fibres it controls. Number of muscle fibres in motor unit varies considerably. The fewer muscle fibres in motor unit, the finer the movement. Coarse movements are associated with larger numbers of muscle fibres per motor unit. 7  Dr Yasser Abdel-Wahab (Module Coordinator) The diagram below shows the skeletal muscle and innervation of the muscle fibers Action potentials in nerve and muscle This diagram shows the difference between action potentials in nerve axons, skeletal muscle, multipotent smooth muscle, and cardiac muscle.  Action potentials (APs) are essential for signaling in nerves and muscle.  APs move along nerves and muscle by propogation.  Resting membrane potential in muscle is between -85 and - 90 mV compared to -70 in axons, but have a similar threshold for firing of APs compared to nerve axons.  APs last longer in muscle tissue (skeletal muscle ~7.5 msec, smooth muscle ~50 msec , and cardiac muscle ~ 250-300 msec).  In muscle tissue APs travel (are propogated along membrane) much slower (3-5 m/sec) than propogation of APs in neurons. Structure and function of skeletal muscle Skeletal musculature Makes up 40-50% of body weight. Largest organ system in body. Contraction is main function. Responsible for all communication with surroundings. Supplies heat. Sarcomere Elementary motor of skeletal muscle. Bounded by Z-lines (disks). Mainly contains contractile proteins: actin, myosin and tropomyosin-troponin. Also contains myoglobin (for CO2 transport). Myofibrils Chains of sarcomeres lined up end to end. Many bundled in parallel within muscle cell. Muscle fibre Bundle of muscle cells lying in parallel. Muscle 8  Dr Yasser Abdel-Wahab (Module Coordinator) Bundle of muscle fibres sheathed in connective tissue. Alignment of thick (myosin) and thin (actin) filaments for contraction myosin Actin and myosin molecules form a lattice of parallel overlapping thin and thick filaments. Each thin filament is surrounded by three thick filaments (see right). Each thick filament is surrounded by six thin filaments (see right). Proper alignment of these filaments is ensured by two proteins: actin – Titin – Nebulin The diagram below shows the layout of actin, myosin, titin and nebulin Titin Giant elastic molecule; largest known protein Single molecule stretches from one Z line to the next M line. Stabilizes position of contractile filaments. Returns stretched muscles to resting length. Nebulin Giant inelastic molecule. Lies alongside thin filaments and attached to Z line. Helps align actin filaments of sarcomere. Sliding filament mechanism of muscle contraction When skeletal muscle fibre (cells) contracts: 1. H bands (contain thick filaments only) and I bands (contain thin filaments only, between A bands of adjacent sarcomeres) get smaller. 2. Zones of overlap get larger (overlapping myosin and actin filaments). 3. Z lines move closer together. 4. Width of A bands remains constant length (thick fibers of myosin stay same length). 5. Thin filaments slide towards centre of the sarcomere (i.e. towards centre of A band, the M line) alongside thick filaments. Sarcomere thus get shorter as Z-line disks between adjoining sacromeres move closer together, this causes muscle to shorten (contract). The diagram below shows these zones and line in relaxed and contracted muscle The M line is the central part of each thick filament and stabilizes position of thick filament 9  Dr Yasser Abdel-Wahab (Module Coordinator) This diagram (below) shows the layout of the thick and thin filaments in the myofibrils and the actin and myosin molecules Thin filaments are made up of F actin, tropomyosin and troponin  F actin – a twisted strand of 300–400 globular molecules of G actin. G actin contains active site which binds to myosin head of thick filament.  Tropomyosin – protein strand covering several G actin active sites to prevent myosin binding.  Troponin – a 3 subunit globular protein. One subunit binds to middle of tropomyosin strand, while the second binds to G actin to hold tropomyosin and G actin together. Third subunit binds calcium ions which are low in resting muscle and increase during stimulation for contraction. Thick filaments contain ~500 myosin molecules made up of 2 twisted myosin subunits. The tail region is bound to other myosin molecules in these filaments. Two globular protein subunits make up the myosin head which projects outwards towards thin filaments. The head is hinged to allow it to pivot either towards or away from the M line during contraction. Muscle tension Force created by contracting muscle. Load Weight or force opposing muscle contraction. Molecular basis of muscle contraction There are six molecular steps involved in the contraction of muscle as illustrated in the diagrams below 1. In active contraction state (rigor) the myosin head is bound to G actin active site and lies at 45o angle relative to thick filament. 2. ATP generated from mitochondrial metabolism binds to the nucleotide binding site of myosin, and this causes myosin to detach from G actin active site. 10  Dr Yasser Abdel-Wahab (Module Coordinator) 3. ATPase activity of myosin converts ATP to ADP and a phosphate group, which gives energy to move the myosin head. 4. The myosin head move to a 90o angle compared to thick filament and binds weakly to the next G actin active site of the thin filament. ADP and phosphate remain bound to the myosin head (this is the relaxed state). 5. The myosin head releases the phosphate group and the head rotates on it hinge towards the M line moving the attached thin filament towards the M line. This is known as the power stroke. 6. At the end of this stroke the myosin head releases the ADP and binds tightly to the G actin active site. The process then returns to step 1 and repeats. The regulatory role of tropomyosin and troponin in contraction In the relaxed state troponin holds tropomyosin over the active site of G actin to prevent myosin binding tightly to the thin filaments. When the muscle is stimulated to contract Ca2+ concentration in the sarcomeres rapidly increase and Ca2+ binds to the third subunit of the troponin molecule. This causes the troponin to change the shape of tropomyosin exposing the active site of G actin. The power stroke can then occur allowing movement of the actin thin filaments towards the centre of the sacromere (M line). Summary of excitation-coupling This diagram summarizes the initiation and termination of contraction and the steps involved 11  Dr Yasser Abdel-Wahab (Module Coordinator) Muscle excitation and contraction 1. Action potential in somatic motor neuron arrives at axon terminal. 2. Voltage-gated calcium channels open. Ca2+ entry triggers exocytosis of ACh-containing synaptic vesicles. 3. ACh diffuses into synaptic cleft and binds with nicotinic receptors on motor end plate of muscle. 4. ACh binding opens a non-specific cation channel. Both Na+ and K+ move through the channel in response to their electro-chemical gradients. Net influx of positive charge depolarizes the muscle membrane, creating an end-plate potential. 5. The end-plate potential is always above threshold and always results in a muscle action potential. 6. The action potential at the neuromuscular junction spreads along muscle fibre membrane, moving into the interior of the fibre via the T-tubules. 7. The action potential in the T-tubule activates dihydropyridine receptors. The DHP receptors open Ca2+ channels in the membrane of the sarcoplasmic reticulum. 8. Ca2+ diffuses out of the sarcoplasmic reticulum and binds to troponin, pulling tropomyosin away from the myosin-binding site. This action allows myosin to release inorganic phosphate from ATP hydrolysis and complete its power stroke. 9. At the end of the power stroke, the mysosin crossbridge releases ADP and remains tightly bound to actin. Myosin must bind an ATP molecule in order to release from this rigor state. 10. The muscle fibre relaxes when Ca2+ releases from troponin, and tropomyosin again blocks the myosin-binding site. Calcium is transported back into the sarcoplasmic reticulum via Ca2+-ATPase. 11. The myosin ATPase hydrolyses ATP to ADP and inorganic phosphate, which both remain bound to the myosin head. The myosin swivels and binds to a new actin molecule, ready to execute its next power stroke. Fast and slow muscles Contraction speed Muscles vary in contraction speed. Specialized function reflects speed of contraction. Slow-contracting (slow-twitch) muscles Involved with maintaining posture. Fibres contain the red oxygen-storing pigment myoglobin, as such, often called red muscles. Good blood, hence oxygen supply. Many mitochondria and high respiratory capacity. Can contract for prolonged periods without fatigue Fast-contracting (fast-twitch) muscles Fibres contain less myoglobin, as such often called white muscles. Poorer blood supply than redmuscles. Few mitochondria and low respiratory capacity. Extensive sarcoplasmic reticulum (hence greater capacity for Ca2+ storage and reabsorption) and high ATPase activity. Can contract rapidly though fatigue easily 12  Dr Yasser Abdel-Wahab (Module Coordinator) Skeletal muscle contraction Threshold stimulus Minimal strength needed to cause contraction Impulse in motor neuron usually releases enough ACh to bring the muscle fibres in its motor unit to threshold. All-or-none response If muscle fibre exposed to stimulus of threshold or above, responds to fullest extent. Increasing strength of stimulus does not affect degree to which fibre contracts If fibre contracts it does so fully Though it contracts fully it may not shorten fully. Stimulation and recording of muscle contraction Electrical stimulus of isolated muscle is called a myogram. If muscle exposed to single stimulus of sufficient strength to activate some motor units, muscle contracts and immediately relaxes. Single contraction, lasting only a fraction of a second called a twitch. Delay between stimulation and response termed latent period. Muscle has a refractory period, i.e. muscle unresponsive for short period after first twitch. Summation Force a muscle fibre can generate is not limited to maximum force of single twitch Multiple stimuli of increasing frequency do not allow muscle to completely relax before next stimulus. Forces of individual twitches combine by process of summation. A forceful, sustained contraction lacking even partial relaxation is called a tetanic contraction. The diagram below shows the temporal events involved in muscle contraction The action potential propagates along the axons from CNS and arrives at the terminal at the neuromuscular junction. The released Ach causes influx of Na+ and K+ into muscle fibre causing action potential in the muscle fibre. The action potential travels throughout muscle fibre and causes release of Ca2+ from sacroplasmic reticulum into sarcoplasm. Ca binds to troponin and allows myosin-actin binding and contraction as mentioned earlier. 13  Dr Yasser Abdel-Wahab (Module Coordinator) Stimulation and multiple stimulation of contraction of muscle A single contraction-relaxation phase is known as a twitch but is not enough to produce the desired overall contraction in skeletal muscle. Treppe – occurs when stimulus to contract arrives straight after relaxation phase has finished and this causes the maximum tension of the next contraction to be slightly larger. Wave summation – this occurs when the stimulus to contract arrives before relaxation of the last phase of contraction has completed and causes a more powerful contraction with higher tension. Incomplete tetanus – If numerous stimulus arrive in wave summation pattern the muscle tension will eventually reach a maximum with further stimulus unable to increase this tension. Complete tetanus – This occurs when the rate of muscle stimulation increases such that the relaxation phase cannot start and tension steadily increases to a maximum. The sarcoplasmic reticulum can not reabsorb Ca2+ in this state of contraction. Complete tetanus causes most muscle contractions. Effects of repeated stimulation on muscle contraction are shown in the diagrams below The diagram below show the changes in muscle metabolism at rest, during peak activity and during recovery 14  Dr Yasser Abdel-Wahab (Module Coordinator) At rest muscle mitochondria generate ATP from nutrients and O2 which is then used to convert creatine to creatine phosphate and glucose to glycogen as energy reserves. During peak activity creatine phosphate is broken down to creatine and glycogen to glucose which allow generation of ATP. This gives energy to the muscle for contraction. Lactic acid is produced from pyruvic acid and levels of lactic acid build up in active muscle and enters blood to allow pH of cells to remain stable. During recovery, lactic acid is converted to pyruvic acid and ATP allows conversion to glucose and glycogen. ATP levels are built up by mitochondrial metabolism of nutrients and more creatine phosphate is generated to allow build of energy reserves again. Muscle tension and control Muscle tension relates to resting sarcomere length and the effects of sarcomere length on muscle tension are illustrated below Most resting muscle fibers will not be compressed or stretched to the extent of (d) and (e) of this diagram. In (a) the maximum number of myosin-actin cross bridges can form which produces high tension. In (b) the stretching of the sarcomere reduces the size of the zone of overlap which means less myosin heads can bind to actin, thus reducing tension. In (c) the sarcomere is slightly compressed and the thin filaments overlap, interfering with ability to form cross bridges and thus reducing tension. The diagram below show the difference in internal and external tension (REDRAW) Internal tension is that produced in the myofibrils of muscle External tension is that in the extracellular fibers and tendons of muscle and this tension is applied by the change in internal tension of the internal muscle fibres. In a twitch (a) the contraction changes the muscle myofibril tension but starts to relax 15  Dr Yasser Abdel-Wahab (Module Coordinator) before the tension is fully transferred to the fibers and tendons (external tension). In tetanus (b) the internal tension reaches maximum and remains high allowing transfer of tension to the surrounding muscle fibers and tendons thereby increasing external tension. The diagram below shows the effects of motor units on muscle tension Muscles contain numerous muscle fibers which are innervated by numerous motor neurons (a). Thus the stimulation of different muscle fibers at different times can still generate increase in overall muscle/tendon tension (b). So one muscle fibre may be relaxing while another is contracting within the entire muscle. Muscle performance, fatigue and the recovery period Performance Can be considered in terms of: – Sheer power Maximum amount of tension produced by particular muscle or muscle group. – Endurance Amount of time for which individual can perform particular activity. Depends on: – Types of muscle fibres in muscle. – Physical conditioning or training. Fatigue When a skeletal muscle fibre can no longer contract despite continued neural stimulation. May be caused by: – Exhaustion of energy reserves. – Build up of lactic acid, causing lowering of pH which prevents muscle fibres from responding to stimulation. – Interruption of blood supply. – Exhaustion of acetylcholine (rare). Recovery period Interval taken to return conditions inside muscle to pre-exertion levels. Muscle’s metabolic activity focuses on: – Removal of lactic acid. – Replacement of intracellular energy reserves. 16  Dr Yasser Abdel-Wahab (Module Coordinator) Isotonic and Isometric contractions Muscular system integration with other body systems The chart below summarizes the connections between muscle system and other body systems 17  Dr Yasser Abdel-Wahab (Module Coordinator) Reading Lists:  Martini FH & Nath JL, Fundamentals of Anatomy and Physiology, San Francisco, Pearson Benjamin Cummings. Martini’s Fundamentals of Anatomy and Physiology was specially selected for this module on the basis of the quality of the textbook, the inclusion of the valuable Fundamentals of Anatomy and Physiology. It comes with Interactive CD-ROM and supporting WWW site (freely accessible to students purchasing this text). 18