Muscle Physiology PDF

Muscle Physiology (Chapter 12) I. Before you begin, make sure you have mastered the following topics: A. Terminology: myo, mys = muscle; sarco = muscle flesh B. Types of muscle tissue; where each is found; voluntary or involuntary; striated or not 1. Skeletal...

Muscle Physiology (Chapter 12) I. Before you begin, make sure you have mastered the following topics: A. Terminology: myo, mys = muscle; sarco = muscle flesh B. Types of muscle tissue; where each is found; voluntary or involuntary; striated or not 1. Skeletal 2. Smooth 3. Cardiac C. Muscle mechanics 1. Muscles work on a lever system; only pull, never push, therefore muscles must be arranged around joints in specific ways to facilitate opposing movements 2. Antagonistic pairs a) Flexors / flexion – bending a limb at a joint or reducing the angle of a joint b) Extensors / extension – straightening a limb at a joint or increasing the angle of a joint c) Abductors and adductors D. Structure of a skeletal muscle (fig. 12.1) 1. A whole skeletal muscle consists of connective tissue wrapped around skeletal muscle fibers 2. Connective tissue – binds muscle fibers together into a bundle called a muscle, and anchors muscle in place a) Whole muscle wrapped in sheet of dense irregular connective tissue b) Connective tissue penetrates muscle and divides it into visible bundles of muscle fibers called fascicles (1) Connective tissue then penetrates each fascicle and separates it into muscle fibers (cells) (2) Tendons are a continuation of connective tissue around muscle c) Skeletal muscle tissue is composed of individual skeletal muscle fibers (1) A single skeletal muscle cell = skeletal muscle fiber (2) Multinucleated (3) Very long (up to 12 inches) and thin (microscopic) (4) Striated in appearance (as is cardiac muscle) E. Terms relating to an individual skeletal muscle fiber (fig. 12.2, 12.3): YOU MUST KNOW THESE TERMS BEFORE COMING TO CLASS 1. Sarcoplasm 2. Sarcolemma 3. Sarcoplasmic reticulum 4. T-tubules 5. Myofibrils 6. Sarcomere Page 1 ©2019 Melaney Birdsong Farr  7. Myofilaments a) actin thin filaments b) myosin thick filaments 8. Your objective is to be able to ‘build’ a whole skeletal muscle from the microscopic to the gross structure, using all appropriate terms. II. Innervation and blood supply to skeletal muscle: nerves & blood vessels travel through the connective tissue to deep in the interior of muscle A. Each muscle fiber is surrounded by blood capillaries; muscle fibers need good blood supply – demand lots of nutrients and oxygen for contraction B. Each muscle fiber makes contact with one neuron in one spot (fig. 12.8) 1. Neuromuscular junction (NMJ) – synapse between a neuron and a muscle fiber 2. A skeletal muscle fiber contracts only when stimulated by neurotransmitter released (due to an AP) from a motor neuron of the somatic (voluntary) division of the peripheral nervous system (fig. 11.13; 11.15) III. Histology of skeletal muscle (fig. 12.33a) A. Components of a skeletal muscle fiber: (fig. 12.2) 1. Has similarities to other eukaryotic cells, important differences, and a different appearance 2. Plasma membrane in skeletal muscle cells (sarcolemma) has T (transverse) tubules – invaginations of plasma membrane that extend into muscle fiber 3. Sarcoplasm = cytoplasm in skeletal muscle cells a) single fiber has many nuclei in sarcoplasm b) stores glucose as glycogen (how animals store glucose) c) contains many mitochondria (why?) d) contains myoglobin (protein similar to hemoglobin) – binds to and stores a small amount of oxygen; makes muscle red e) sarcoplasmic reticulum (SR) = smooth ER in skeletal muscle cells; system of membrane tubes that wrap internal cellular structures; packed with calcium (in lateral sacs of SR) f) myofibrils – rod-shaped, submicroscopic (1-2 micrometers in diameter) protein structures; run throughout the long axis of a muscle fiber -- ©2019 Melaney Birdsong Farr 2  B. Myofibril structure (in detail) – surrounded by sarcoplasmic reticulum; contain two kinds of myofilaments (short, thread-like protein structures) organized into sarcomeres (fig. 12.3) 1. Myofilament components of a sarcomere: (fig. 12.5) a) thin filaments (fig. 12.4) (1) made mostly of actin protein (2) a long thin filament with actin active sites (also called myosin binding sites) (handles) (3) thin filaments also have two other associated proteins: troponin, tropomyosin (will cover later) b) thick filaments (fig. 12.5) (1) made of myosin protein (2) thicker rod with myosin heads (hands) sticking out (3) myosin heads can bind to actin active sites to form a crossbridge 2. The arrangement of these proteins (sarcomere) gives skeletal muscle its striated appearance: thin filaments on the outside, thick filaments on the inside (fig. 12.3) C. Sarcomere structure (fig. 12.3) 1. Sarcomere = the functional unit of skeletal muscle tissue 2. Ends of a single sarcomere are Z-lines 3. Actin (thin) filaments attach to Z-lines and extend toward center of sarcomere, but do not touch one another 4. Myosin (thick) filaments ‘float’ in middle of sarcomere 5. Sarcomere pattern: a) A-band = region in which actin and myosin overlap (dark) b) I-band = region which has actin thin filaments only (light) c) H-zone = region which has myosin thick filaments only (in center of each A-band) d) M-line = narrow, dark band in the center e) titin proteins attach from the Z-line to the M-line, but are generally not visible Page 3 ©2019 Melaney Birdsong Farr  f) NOTE: A-bands and I-bands (respectively) are the visible dark and light striations g) A chain of sarcomeres makes up a myofibril (think ‘boxcars on a train’) h) Label structures 1-8 on the figure below, using the following terms: M-line, actin thin myofilaments, myosin thick myofilaments, Z-line, H-zone, A-band, I-band, sarcomere IV. The sliding filament theory - molecular mechanisms of contraction ANIMATION: Crossbridge cycling A. How a sarcomere contracts: 1. To contract (shorten) a sarcomere (and therefore shorten muscle fiber), myosin heads “hands” must grab actin active site “handles”, and pull (fig. 12.6) 2. This will shorten the whole sarcomere 3. When an active site “handle” and a head “hand” are attached, it is called a crossbridge B. Steps in crossbridge cycling (fig. 12.7) 1. Attachment of the crossbridge: myosin head attaches to actin active site 2. Inorganic phosphate is released -- ©2019 Melaney Birdsong Farr 4  3. Powerstroke = movement of the crossbridge: crossbridge pivots due to myosin head movement 4. Release of ADP 5. Detachment of the crossbridge from the thin filament and a) re-energizing the crossbridge for the next cycle: the myosin head released and is re-energized (re-cocked); ATP required here b) start the process over C. NOTES 1. length of sarcomere shortens, but 2. length of myofilaments does not change 3. H-zone and I-band may disappear during contraction, but length of A band does not change much (fig. 12.6) 4. Many sarcomeres contracting together shortens an entire myofibril, which may shorten the whole muscle fiber, which may shorten the whole muscle fascicle, which may shorten the whole muscle INTERACTIVE ACTIVITY: Crossbridge cycling D. Excitation-contraction coupling: How is muscle contraction triggered by the nervous system? Role of troponin, tropomyosin, and calcium in muscle contraction: control of skeletal muscle activity 1. Nerves (specifically, axons of somatic motor neurons) go directly to the cell membrane of muscle fiber at NMJ (fig. 11.15; fig. 12.8) 2. Skeletal muscle fiber must have direct neural stimulus to contract 3. Membrane excitation: (fig. 11.15; fig. 12.8) a) Nervous system portion of membrane excitation (1) action potential (AP) on axon terminal of motor neuron ⇒ (2) causes acetylcholine secretion from axon terminal (due to opening voltage-gated Ca++ channels and Ca++ influx at the axon terminal) ⇒ Page 5 ©2019 Melaney Birdsong Farr  b) Muscular system portion of membrane excitation (1) acetylcholine binds to receptors (ligand-gated Na+ channels) on motor end plate of skeletal muscle plasma membrane (sarcolemma) ⇒ (2) depolarizing graded potential generated on sarcolemma ⇒ (3) If threshold is reached, AP is generated ⇒ (4) AP transmitted down T tubules ⇒ (5) AP reaches sarcoplasmic reticulum c) Contraction cycle begins: (1) Release of calcium from SR: AP causes calcium (Ca+2) release from the SR of the muscle fiber into the sarcoplasm (cytoplasm) (fig. 12.10) (2) Exposure of active sites: calcium allows muscle contraction to occur by exposing the actin active sites (fig. 12.9) (3) When calcium is present, it “lowers” the tropomyosin barrier by binding to it at small fibers called troponin (on/off switch) fibers (4) NOTE: Under ‘unstimulated’ circumstances, the actin active sites are covered with a protein called tropomyosin (barrier), which prevents crossbridge formation (5) Now the actin active sites are available for the myosin heads to form a crossbridge. d) Crossbridge attachment e) Phosphate falls off f) Powerstroke: pivoting of myosin head g) ADP falls off h) Crossbridge detachment and myosin reactivation: hands release and re-energize for the next powerstroke (requires ATP) (1) attachment, movement, and release happens many times during a single contraction (crossbridge cycling) (2) when calcium in sarcoplasm returns to normal levels, contraction stops -- ©2019 Melaney Birdsong Farr 6  i) Relaxation sequence of events: (1) AP on axon ends (2) acetylcholine previously released must be destroyed NOTE: acetylcholine is destroyed by an enzyme present at the neuromuscular junction (acetylcholinesterase), so that the fiber will not be continuously stimulated (3) APs on sarcolemma will stop without acetylcholine to depolarize (4) Ca+2 is actively pumped into SR for storage – ATP required (5) with Ca+2 removed from troponin, tropomyosin barrier is up and prohibits crossbridge formation (6) actin (thin) filaments slip back into resting position (7) sarcomere stays relaxed until another AP arrives INTERACTIVE ACTIVITY: The Neuromuscular Junction INTERACTIVE ACTIVITY: Excitation-Contraction Coupling V. Mechanics of single-fiber skeletal muscle contraction A. Twitch = response of muscle fiber to a single action potential (fig. 12.11) 1. Latent period – after AP but before muscle response 2. Contraction time 3. Relaxation time B. Tension and load 1. Tension = the force exerted on an object by a contracting muscle; does not always lead to shortening 2. Load = the force exerted on the muscle by the object 3. Tension and load oppose one another C. Isometric contraction – muscle develops tension but does not measurably shorten; iso = same, metric = length (fig. 12.12a) 1. Supporting in constant position Page 7 ©2019 Melaney Birdsong Farr  2. Sketch an isometric twitch above. Label the X- and Y-axes and the latent period, contraction phase, and relaxation phase. D. Isotonic contraction – muscle shortens, moving a constant load, moving the body (fig. 12.12b) VI. Whole muscle contraction: how is amount of tension in a whole muscle controlled? A. SUMMATION: if a muscle fiber is not allowed time to completely relax between contractions the Ca++ release from the first AP and the second AP are added to one another, leading to SUMMATION – a sustained average tension in the fiber as the twitches are added to one another (fig. 12.16) 1. incomplete (unfused) tetanus a) stimuli come so rapidly that the muscle can only partially relax between stimuli b) results in sustained high level contraction 2. complete (fused) tetanus a) stimuli come faster still b) no relaxation at all B. RECRUITMENT (or motor unit summation) of muscle fibers (fig. 12.18, 12.19) 1. Recruitment = how many fibers contract a) The # of muscle fibers contracting depends on the number of motor neurons firing -- ©2019 Melaney Birdsong Farr 8  b) Motor unit = one motor neuron + the skeletal muscle fibers it innervates (fig. 12.18) c) The number of motor neurons firing is determined (involuntarily) by the central nervous system d) Muscles are divided into motor units, with different numbers of fibers depending on the activity of the muscle (1) Precise movements: ~10 muscle fibers innervated by one neuron (2) Gross movements: ~ 500 muscle fibers innervated by one neuron e) In order to increase the tension of a whole muscle, more motor units are recruited = RECRUITMENT (motor unit summation); usually smaller motor units are recruited first – the size principle 2. Tonic contraction (tonus or tone) a) Sustained, partial contraction of portions of muscle in response to stretch receptors b) At any given time, some fibers are contracting in a muscle, while others are relaxed. This tightens muscle, but doesn’t produce (gross) movement. Even relaxed muscles have tone. c) Motor units alternate firing and relieve each other. Tonus can be maintained for a long time. d) Tone is essential for maintaining posture e) Muscle with less than normal tone = flaccid (1) denervation atrophy – damage to nerve – muscle eventually replaced with connective tissue; irreversible (2) disuse atrophy – bedridden or cast; can be reversed after short durations (4 months); lose muscle after 2 years Page 9 ©2019 Melaney Birdsong Farr VII. Types of muscle fibers A. Types of skeletal muscle fibers– different fibers have different capabilities and metabolic activities (fig. 12.25; table 12.1) 1. Fast-twitch v. slow-twitch fibers: maximal velocities of shortening; rate of crossbridge cycling is about 4X as fast in fast fibers, as determined by different types of myosin in the fiber 2. Glycolytic v. oxidative fibers: preferred pathway used to form ATP a) oxidative fibers: (1) lots of mitochondria and thus high capacity for oxidative phosphorylation (2) require lots of blood flow for oxygen and fuel (3) contain lots of myoglobin, making the fibers red (4) usually smaller diameter (5) often called red muscle fibers b) glycolytic fibers (1) fewer mitochondria (2) larger stores of glycogen (3) fewer blood vessels supplying each fiber (4) little to no myoglobin (5) often called white muscle fibers 3. Three types of fibers: a) Slow-oxidative/ SO (smallest diameter) – postural muscles of the back; first recruited; least powerful; last longest b) Fast-oxidative (intermediate diameter) – rare; recruited next; intermediate strength; intermediate longevity c) Fast-glycolytic/ FG (largest diameter) – biceps brachii, eye muscles; last recruited; strongest; first to fatigue -- ©2019 Melaney Birdsong Farr 10 VIII. Skeletal muscle energy metabolism (fig. 12.22), when muscles are active ANIMATION: Muscle Metabolism A. General information: ATP is source of energy; skeletal muscle needs lots of it! Obtaining ATP from food is slow; so, several reserves exist B. Sources of energy for muscle contraction 1. Myosin heads left in high energy position, ready for powerstroke 2. Creatine phosphate + ADP ⇒ creatine + ATP = phosphorylation of ADP (very rapid, but only available for 1 minute at brisk walk or 6 seconds of sprinting); Enzyme needed is CPK (creatine phosphokinase); CPK spills out of damaged muscle cells; can be used diagnostically 3. Small quantity of oxygen bound to myoglobin, so aerobic cellular respiration may be possible as the cardiovascular and respiratory systems catch up. 4. Break down glycogen (this is the major source at the beginning of exercise, first 5-10 minutes) to glucose, then aerobic cellular respiration (glycolysis and oxidative phosphorylation). 5. Blood glucose breakdown by glycolysis and oxidative phosphorylation (next 30 minutes). 6. After this, energy is primarily from fatty acid breakdown (glycogenolysis) (glycolysis) (anaerobic respiration) glycogen⇒⇒⇒⇒⇒⇒glucose ⇒⇒⇒⇒⇒pyruvate + ATP ⇒⇒⇒⇒⇒⇒⇒⇒⇒⇒⇒⇒⇒ lactic acid + ATP ⇓ ⇓ (Krebs and oxidative phosphorylation) ⇓ requires O2 ⇓ CO2 + H2O + lots of ATP 7. NOTES: a) breakdown of glycogen (glycogenolysis) to glucose requires no oxygen b) glycolysis requires no oxygen and produces a small amount of ATP c) anaerobic respiration requires no oxygen and produces a small amount of ATP Page 11 ©2019 Melaney Birdsong Farr  d) fatigue occurs due to lack of ATP and buildup of lactic acid; lactic acid buildup is NOT a major cause of muscle soreness e) Krebs cycle and oxidative phosphorylation require oxygen and together produce lots of ATP f) Recovering from muscle activity (1) oxygen bound to myoglobin and hemoglobin must be replaced (2) creatine phosphate must be replaced (via phosphorylation with ATP) (3) lactic acid must be oxidized back to glucose by the liver (requires oxygen) (4) glycogen levels are low and must be replaced (5) nutrients (glucose) and energy (for anabolic reactions) and oxygen are therefore required even after muscle activity (6) continue to breathe deeply and rapidly after exertion to repay oxygen debt from replacing creatine phosphate and glycogen g) Body also generally has to be cooled after muscle activity, which is energetically expensive. Of the energy released as glucose is broken down, only about 40% is used for muscle contraction; rest released as heat; this is why shivering works to heat up the body! IX. Clinical notes A. Rigor mortis 1. no ATP being made after death, so... 2. myosin “hand” can’t detach from actin “handle” and 3. calcium can’t get back into SR and continues to leak from ECF and SR into sarcoplasm 4. causes sustained muscle contraction – stiff as a board. 5. stiffness leaves body 12-15 hours after death, as cells begin to decompose B. Poliomyelitis – virus destroys motor neurons; result? VACCINE C. Cramps – APs on motor neurons fire at abnormally high rates (often due to ion imbalances); causes involuntary tetanic contractions -- ©2019 Melaney Birdsong Farr 12  D. Muscular dystrophy – genetic disease, more common in males; progressive degeneration of skeletal and cardiac muscle fibers; weakens muscles and leads to death from respiratory or cardiac failure; exercise worsens the situation; problem seems to be an error in a cytoskeletal protein E. Myasthenia gravis – autoimmune disease that causes destruction of motor end plates; lose ACh receptors F. Tetanus – Clostridium tetani, a common soil bacterium, produces a neurotoxin in anaerobic conditions; VACCINE G. Botulism – often contracted from improperly canned foods; toxin produced by Clostridium botulinum in anaerobic conditions, prevents release of Ach; flaccid paralysis; Botox cosmetic H. Chemicals that affect neuromuscular junction 1. curare – blocks receptors on sarcolemma; causes asphyxiation because of paralysis of diaphragm 2. some nerve gases (including sarin gas) and pesticides – inhibit acetylcholinesterase; effect? X. Skeletal muscle adaptation to exercise A. Development of skeletal muscle 1. Embryonically, mitosis occurs ⇒ many small (uninucleate) muscle cells (myoblasts) ⇒ cells fuse to form long, multinucleated muscle fibers (a process called syncytium) 2. Once the cells have fused into muscle fibers, fibers cannot undergo mitosis, with the exception of satellite cells (muscle stem cells); any repair or regeneration is from the few satellite (stem) cells present 3. At birth, child has approximately all the muscle fibers he will ever have B. Increase in size of a whole muscle in adults 1. Results from increasing length and diameter of muscle fibers, not from increasing the number of muscle fibers 2. In adult, muscles hypertrophy only if contracted to ~ 75% maximum tension (strength training); such high-intensity exercise produces … a) increases # of actin and myosin filaments and myofibrils, not # of fibers Page 13 ©2019 Melaney Birdsong Farr  b) mostly white fibers (fast-glycolytic) that enlarge (little myoglobin, make ATP anaerobically, but large and strong) c) only a few contractions at a time are necessary or possible d) work out muscle groups every other day; muscles grow during rest and recovery 3. Weak activity (aerobic exercise) (