Muscle Physiology, Sliding Filament Theory, Slides of Human Physiology

Download Muscle Physiology, Sliding Filament Theory and more Slides Human Physiology in PDF only on Docsity! 1 Page 1 M u s c le P h y s io lo g y Muscle Physiology Skeletal Muscle Anatomy: Muscle fibers (= individual muscle cells): • Multi-nucleated (mitosis sans cytokinesis) • Sarcolemma (= plasma membrane + collagen fibers) • Sarcoplasm (= cytoplasm;  mitochondria) • Myofibrils (contractile elements): • Actin filaments (thin) • Myosin filaments (thick) Sarcomere Z Z Bare zone M Titin: Filamentous structural protein (“springy”) I band Isotropy (Gr.) A band Anisotropy (Gr.) Dystrophin: Anchors myofibril arrays to cell membrane Muscular dystrophy Randall et al. (Eckert: Animal Physiology, 5th ed.) – Figure 10.2 / 10.3 Sliding Filament Theory (Huxley and Huxley – 1954): Contraction results from sliding action of inter-digitating actin and myosin filaments Evidence? Myosin head interacts with actin (cross-bridging) Each cross-bridge generates force independent of other cross-bridges Thus Total tension developed by sarcomere proportional to number of cross-bridges (proportional to filament overlap) Muscle Physiology Randall et al. (Eckert: Animal Physiology, 5th ed.) – Figure 10.8 Length-tension relationship Muscle Physiology Sliding Filament Theory (Huxley and Huxley – 1954): Randall et al. (Eckert: Animal Physiology, 5th ed.) – Figure 10.8 / 10.9 Muscle Physiology Length-tension relationship Randall et al. (Eckert: Animal Physiology, 5th ed.) – Figure 10.8 / 10.9 Sliding Filament Theory (Huxley and Huxley – 1954): Muscle Physiology Length-tension relationship Randall et al. (Eckert: Animal Physiology, 5th ed.) – Figure 10.8 / 10.9 Sliding Filament Theory (Huxley and Huxley – 1954): 2 Page 2 Muscle Physiology Length-tension relationship Randall et al. (Eckert: Animal Physiology, 5th ed.) – Figure 10.8 / 10.9 Sliding Filament Theory (Huxley and Huxley – 1954): Maximum Contraction Strength: ~ 50 lbs. / inch2 Normal resting length of skeletal muscle Muscle Physiology Length-tension relationship Randall et al. (Eckert: Animal Physiology, 5th ed.) – Figure 10.8 / 10.9 Sliding Filament Theory (Huxley and Huxley – 1954): The geometry of myofilaments in a sarcomere strongly affects the contractile properties of the muscle Muscle Physiology Randall et al. (Eckert: Animal Physiology, 5th ed.) – Spotlight 10.1 1) Myosin: • Two heavy chains (tail) • Four light chains (head) • Actin-binding sites • ATPase activity • Myosin filament composed of 200+ individual myosin molecules (~1.6 m in length) 2) Actin: • Two double-stranded helixes of G-actin polymers woven to form F-actin (~ 1 m in length) • ADP attached to G-actin (active site) • Tropomyosin: Spiral around F-actin; cover active sites • Troponin: Attaches tropomyosin to F-actin Muscle Physiology Myofilament Anatomy: Guyton & Hall (Textbook of Medical Physiology, 12th ed.) – Figure 6.5 1) Myosin: • Two heavy chains (tail) • Four light chains (head) • Actin-binding sites • ATPase activity • Myosin filament composed of 200+ individual myosin molecules (~1.6 m in length) 2) Actin: Muscle Physiology Myofilament Anatomy: Guyton & Hall (Textbook of Medical Physiology, 12th ed.) – Figure 6.5 Troponin (sub-units): 1) Troponin C: Binds calcium (up to 4 Ca++) 2) Troponin T: Binds tropomyosin 3) Troponin I: Binds actin (covers active site on actin) Walk-Along Theory: Ca++ enters sarcoplasm; tropomyosin shifts Muscle Physiology 5 Page 5 Neuromuscular Junction: Neuron  Muscle fiber M o to r N e u ro n Muscle Fiber Subneural cleft ( surface area) Synaptic cleft 2 0 – 3 0 n m STEP 1: Secretion of acetylcholine by nerve terminals Muscle Physiology Excitation – Contraction Coupling: 1 connection / muscle fiber Motor End Plate Guyton & Hall (Textbook of Medical Physiology, 12th ed.) – Figure 7.1 Neuromuscular Junction: M o to r N e u ro n Muscle Fiber Muscle Physiology Excitation – Contraction Coupling: ~ 300,000 A) Small vesicles formed in stoma of neuron; shuttled to axon terminal B) Acetylcholine (ACh) synthesized in terminal; transported into vesicles (~ 10,000 Ach / vesicle) C) Action potential travels down axon; activates voltage-gated Ca++ channels at terminal Ca++ Ca++ D) Ca++ influx triggers vesicles to fuse with membrane (~ 125 vesicles / AP); ACh released E) ACh binds with ACh-gated ion channels at mouth of subneural clefts (muscle fiber) Choline + Acetyl CoA Acetylcholine choline acetyltransferase Nicotinic receptors ACh-gated Ion Channel: • 5 sub-units (2 alpha, 1 beta, 1 gamma, 1 delta); form tubular channel 40 0 -40 -80 mV 0 15 30 45 60 75 mSec • Opening of Ach-gated ion channels produces end plate potential (EPP) • Strong EPP triggers voltage-gated sodium channels (AP generation) Safety Factor: Each AP arriving at neuromuscular junction causes ~ 3x end plate potential necessary to stimulate muscle fiber Acetylcholinesterase (AChE): Deactivates ACh (synaptic cleft) Muscle Physiology MEPPACh = 0.4 mV Excitation – Contraction Coupling: Guyton & Hall (Textbook of Medical Physiology, 12th ed.) – Figure 7.2 • Activation = 2 ACh molecules (bind to alpha units) • Primarily Na+ channel: • (-) charge restricts anions • (-) RMP of muscle fiber favors Na+ influx vs. K+ efflux Pathophysiology: Various drugs / toxins / diseases exist that are capable of enhancing or blocking neuromuscular junction activity Neurophysiology normal Drugs / Toxins - Inhibitors: Botulism (bacterial toxin -  ACh release) Curare (plant toxin – blocks ACh receptors) Nicotine (plant derivative – mimics ACh) Sarin Gas (synthetic – deactivates AChE) Drugs / Toxins - Stimulants: Myasthenia Gravis (“grave muscle weakness”) Autoimmune; destruction of ACh-gated Na+ receptors Treatment = Anti-AChE drugs Result = Paralysis (Weak EPPs) Rare Condition: 1 / 20,000 Can be fatal (diaphragm paralysis) Role of Calcium: Ringer’s Solution Isolated Frog heart stopped beating if Ca++ omitted from bath • Interacts with troponin in thin filament: When Ca++ binds: (uncovers active sites) 2) Troponin I / actin bond weakens 1) Troponin T / I / C bonds strengthen 10-4 Muscle Physiology Excitation – Contraction Coupling: Randall et al. (Eckert: Animal Physiology, 5th ed.) – Figure 10.15 Sidney Ringer (1836 – 1910) Solution: Sarcoplasmic Reticulum For a muscle contraction to occur, there must be a link between electrical excitation and increased intracellular Ca++ levels… Problem 1: Rate of diffusion from Ca++ to interior of cell (~ 25 – 50 m) several orders of magnitude too slow to explain observed latent period AP triggers voltage-gated Ca++ channels in plasma membrane which flood cell with Ca++… Terminal cisterna: Hollow collars around myofibril; neighbor Z lines • Specialized ER; stores Ca++ The only source of regulatory Ca++ in skeletal muscle is from the SR • SR membrane contains Ca++ pumps • Maintain < [10-7 M Ca++] • Calsequestrin: Binds Ca++ in SR • Reduces [gradient] Muscle Physiology Excitation – Contraction Coupling: Randall et al. (Eckert: Animal Physiology, 5th ed.) – Figure 10.12 / 10.15 6 Page 6 Problem 2: A potential difference across the plasma membrane of a muscle fiber affects an intracellular region a fraction of a m deep (Myofibrils 50 – 100 m thick) Solution: Transverse Tubules OK… intracellular Ca++ stores released by AP spreading along surface of muscle cell… Cytoplasmic extensions continuous with plasma membrane (~ 0.1 µm diameter); provide link between plasma membrane and myofibrils deep inside muscle fiber Muscle Physiology For a muscle contraction to occur, there must be a link between electrical excitation and increased intracellular Ca++ levels… Excitation – Contraction Coupling: Guyton & Hall (Textbook of Medical Physiology, 12th ed.) – Figure 7.5 How does Ca++ escape the SR? Ryanodine Receptors: Dihydropyridine Receptors: • Located in T-tubule; voltage-gated Ca++ channels • Only ½ of the ryanodine receptors linked with dihyropyridine receptors Calcium-induced Calcium Release (Positive feedback mechanism) Muscle Physiology Excitation – Contraction Coupling: Randall et al. (Eckert: Animal Physiology, 5th ed.) – Figure 10.25 Plunger Model • Located in SR; Ca++ channels AP Ca2+ pump calsequestrin Transverse tubule - - - - - - - - + + + + + + + + + + + + + + + + - - - - - - - - Muscle Physiology Excitation – Contraction Coupling: Ca2+ pump calsequestrin Transverse tubule Muscle Physiology Excitation – Contraction Coupling: + + + + + + + + - - - - - - - - Ca2+ pump calsequestrin Transverse tubule Clinical Oddity: Malignant Hyperthermia Trigger: Anesthetics (e.g., halothane) Familial tendency… can be tested for by muscle biopsy • Skeletal muscle rigidity Body is only 45% energy efficient; 55% of the energy appears as heat • Spontaneous combustion • Metabolic acidosis (hypermetabolism) Muscle Physiology Excitation – Contraction Coupling: Muscle Energetics: Major processes requiring energy: [ATP] in stimulated muscles = [ATP] in unstimulated muscles - ??? ATP usage: ~ 600 trillion / second • Creatine phosphokinase • ~ 5 – 8 seconds of fuel… (100 m) • Anaerobic respiration • ~ 1 minutes (“poisons” system) (400 m) • Oxidative metabolism (aerobic respiration) • Primary food source = glycogen / lipids (5000 m) 4x 2x 1x Rate: Muscle Physiology 1) Cross-bridging 2) Ca++ and Na+ / K+ pumps Guyton & Hall (Textbook of Medical Physiology, 12th ed.) – Figure 84.1 7 Page 7 Muscle Mechanics: 1) Cross-bridge detachment rate (fast detachment = fast contraction) • Chemical nature of myosin head (Vmax of ATPase) 2) Density of Ca++ pumps (affects clearance of Ca++) 3) Mitochondria # / vasculature (affects oxidative ATP production capacities) Fast Glycolytic Fibers: • Rapid cross-bridge cycling • Rapid Ca++ clearance • Low endurance (anaerobic respiration) • () glycolytic enzyme content • () glycogen reserves Large diameter (powerful) Muscle Physiology Muscle fibers can be divided into two primary types based on anatomical and physiological properties Marieb & Hoehn (Human Anatomy and Physiology, 9th ed.) – Figure 9.14 Slow Oxidative Fibers: • Slow cross-bridge cycling • Slow Ca++ clearance • High endurance • () mitochondria / capillaries • () myoglobin content Small diameter Muscle Physiology Muscle Mechanics: 1) Cross-bridge detachment rate (fast detachment = fast contraction) • Chemical nature of myosin head (Vmax of ATPase) 2) Density of Ca++ pumps (affects clearance of Ca++) 3) Mitochondria # / vasculature (affects oxidative ATP production capacities) Muscle fibers can be divided into two primary types based on anatomical and physiological properties Marieb & Hoehn (Human Anatomy and Physiology, 9th ed.) – Figure 9.14 White Muscle: Muscle dominated by fast fibers (e.g. chicken breast) Red Muscle: Muscle dominated by slow fibers (e.g. chicken leg) Most human muscles contain both types of muscle fibers; proportions differ Fast Fibers Slow Fibers Marathon 18% 82% Runners Swimmers 26% 74% Avg. Human 55% 45% Weight 55% 45% Lifters Sprinters 64% 37% Jumpers 63% 37% • Genetically determined • No evidence that training significantly alters proportions Muscle Physiology Muscle Mechanics: Muscle fibers can be divided into two primary types based on anatomical and physiological properties Muscle Remodeling: Muscle Hypertrophy: Increase in total mass of muscle b) Fiber Hypertrophy (most common) • Increase in myofilament number • Trigger = Near maximal force generation • Increase in muscle fiber number • Trigger: Extreme muscle force generation c) Hyperplasia (rare) a) Lengthening (normal growth) • Sarcomeres added to existing myofilaments Loss of muscle performance ( contractile proteins =  force /  velocity) Causes: Plaster cast Muscle Atrophy: Decrease in total mass of muscle Weeks Years Muscle Physiology Sedentary lifestyle Denervation / neuropathy Space flight (zero gravity) • Discrete muscle fibers • Nervous control (single innervation / fiber) • Location: Iris, piloerector muscles Unitary smooth muscle • Sheets / bundles of muscle fibers • Electronically-coupled (gap junctions) • Multiple controls (e.g., hormonal / spontaneous) Multi-unit smooth muscle Muscle Physiology Types of Smooth Muscle: • Form muscular walls of hollow organs • Location: Walls of viscera Guyton & Hall (Textbook of Medical Physiology, 12th ed.) – Figure 8.1 Smooth Muscle: • Produce mobility (e.g., gastrointestinal tract) • Maintain tension (e.g., blood vessels) • Mono-nucleated cells (20 – 500 m length / 1-5 m width) Properties of Smooth Muscle: Contraction occurs via actin / myosin interaction (ATP) Smooth Muscle – How Does it Differ from Skeletal Muscle? 1) Physical Organization: Dense-bodies: Analogous to Z lines Intermediate Filaments (structural backbone) Gap Junction Mechanical Junction Smooth muscle can operate over large range of lengths (~ 75% shortening possible) • Dispersed / attached to cell membrane Muscle Physiology HOWEVER Smooth muscle appears non-striated • Anchor actin filaments Marieb & Hoehn (Human Anatomy and Physiology, 9th ed.) – Figure 9.27