MHS1102 Lecture 1 Muscle Physiology PDF

MHS1102:LECTURE 1 MUSCLE PHYSIOLOGY  LEARNING OUTCOMES By the end of this lecture you should be able to:  List the characteristic features of skeletal muscle  Describe the structural components of a muscle fibre  Name the major proteins in muscle fibres and state the function of each...

MHS1102:LECTURE 1 MUSCLE PHYSIOLOGY  LEARNING OUTCOMES By the end of this lecture you should be able to:  List the characteristic features of skeletal muscle  Describe the structural components of a muscle fibre  Name the major proteins in muscle fibres and state the function of each  Describe the structures & processes involved in the stimulation & contraction of skeletal muscle fibres  Describe the stages of a muscle twitch  UNIVERSAL CHARACTERISTICS OF MUSCLE  Excitability (responsiveness)  to chemical signals, stretch & electrical changes across plasma membrane  Conductivity  electrical excitation initiates wave of excitation that travels along muscle fibre  Contractility  shortens when stimulated  Extensibility  capable of being stretched between contractions  Elasticity  returns to original rest length after being stretched  SKELETAL MUSCLE  Attached to bone by tendons  external connective tissue layer surrounding muscle tissue is continuous with collagen fibers of tendons  contraction brings about movement across joints  collagen extensible & elastic  stretches slightly under tension & recoils when released  resists excessive stretching & protects muscle from injury  returns muscle to its resting length  contributes to power output & muscle efficiency  SKELETAL MUSCLE  voluntary, striated muscle  voluntary - usually subject to conscious control  striated - alternating light & dark bands due to internal contractile proteins  a muscle cell is a muscle fibre (myofibre) – up to 30 cm in length  LEARNING OUTCOMES By the end of this lecture you should be able to:  List the characteristic features of skeletal muscle√  Describe the structural components of a muscle fibre  Name the major proteins in muscle fibres and state the function of each  Describe the structures & processes involved in the stimulation & contraction of skeletal muscle fibres  Describe the stages of a muscle twitch  STRUCTURAL HIERARCHY OF SKELETAL MUSCLE 1 Structural Level Description A contractile organ, usually attached to bones by Muscle way of tendons. Comprises bundles (fascicles) of tightly packed, long, parallel cells (muscle fibres). Supplied with nerves & blood vessels & enclosed in a fibrous epimysium that separates it from neighboring muscles. A bundle of muscle fibres within a muscle. Supplied Fascicle by nerves & blood vessels & enclosed in fibrous perimysium that separates it from neighboring fascicles. A single muscle cell. Slender, elongated, enclosed in specialized plasma membrane (sarcolemma). Contains Muscle Fibre densely packed bundles (myofibrils) of contractile protein filaments, multiple nuclei immediately beneath the sarcolemma & an extensive network of specialized smooth endoplasmic reticulum (sarcoplasmic reticulum – Ca+ storage). Enclosed in thin fibrous sleeve called endomysium. TABLE 11.1 The Structural Hierarchy of a Skeletal Muscle Copyright© McGraw-Hill Education. Permission required for reproduction or display.  THE SKELETAL MUSCLE CELL/FIBRE  multiple peripheral nuclei  mitochondria between myofibrils  glycogen: carbohydrate stored to provide energy for exercise  myoglobin: red pigment - provides some O2 needed for muscle activity  THE MUSCLE FIBRE  myoblasts: stem cells fuse & form muscle fibres early in development  satellite cells: unspecialized myoblasts between muscle fibre & endomysium  play a role in regeneration of damaged skeletal muscle tissue  THE MUSCLE FIBRE: MYOFIBRILS  attached to the inner surface of sarcolemma  comprise bundles of protein filaments called myofilaments  thin filaments (actin) & thick filaments (myosin)  interactions of thick & thin filaments are responsible for muscle contraction  THE MUSCLE FIBRE  sarcoplasmic reticulum (SR): smooth ER that forms a network around each myofibril  terminal cisterns: dilated end-sacs of SR that cross muscle fibre from one side to the other  cisterns act as Ca+ reservoir - release Ca+ through channels to activate muscle contraction  THE MUSCLE FIBRE  T tubules: tubular infoldings of sarcolemma which penetrate through cell & emerge on other side  Triad: a T tubule & two terminal cisterns associated with it  muscle contraction begins when stored Ca+ released into sarcoplasm  THE MUSCLE FIBRE: SARCOMERES ▪ myofilaments are organised into repeating functional units called sarcomeres ▪ myofibril comprises thousands of sarcomeres ▪ sarcomeres have dark bands (A bands) & light bands (I bands) - striations  THE MUSCLE FIBRE: SARCOMERES  sarcomere - segment from Z line/disc to Z disc  H band contains thick filaments (myosin) at the centre of the sarcomere  I bands contain thin filaments (actin) – no thick filaments  proteins that stabilise the position of thin & thick filaments  proteins that regulate interactions between thin & thick filaments  THE MUSCLE FIBRE: SARCOMERES Subdivisions within sarcomeres: M Line - proteins that connect neighbouring thick filaments H band - region either side of M line - only includes thick filaments Zone of overlap [A band] - thin & thick filaments overlap  LEARNING OUTCOMES By the end of this lecture you should be able to:  List the characteristic features of skeletal muscle √  Describe the structural components of a muscle fibre √  Name the major proteins in muscle fibres and state the function of each  Describe the structures & processes involved in the stimulation & contraction of skeletal muscle fibres  Describe the stages of a muscle twitch SARCOMERES: CONTRACTILE PROTEINS: ACTIN & MYOSIN Actin comprises thin filaments  fibrous (F) actin: two intertwined strands  string of globular (G) actin subunits each with an active site that can bind to the head of myosin molecule  tropomyosin – actin binding protein  molecules block active sites on G actin subunits  troponin - small, calcium-binding protein on each tropomyosin molecule Figure 11.3c  SARCOMERES: ACTIN & MYOSIN  Myosin comprises thick filaments  myosin molecules shaped like a double-headed golf club  two chains intertwined to form a shaft-like tail & double globular head  heads directed outward in a helical array around the myosin bundle  heads on one 1/2 of filament angle to left, heads on other 1/2 angle to right  bare zone - no heads Figure 11.3a, b, d  MYOFILAMENTS: DYSTROPHIN  clinically important protein  links actin in outermost myofilaments to membrane proteins that link to endomysium  transfers forces of muscle contraction to connective tissue leading to tendon  genetic defects in dystrophin result in muscular dystrophy Figure 11.4  MYOFILAMENTS: TITIN  Elastic filaments  titin [connectin]: large protein  runs through core of thin filament & anchors it to Z disc & M line  help stabilize & position the thick filament  prevent overstretching & provide recoil  STRUCTURAL HIERARCHY OF SKELETAL MUSCLE Structural Level Description A bundle of protein myofilaments within muscle fibre; myofibrils collectively fill most Myofibril of cytoplasm. Each surrounded by sarcoplasmic reticulum & mitochondria. Has a banded (striated) appearance due to orderly overlap of protein myofilaments. A segment of myofibril from one Z disc to the next in the striation pattern. Hundreds Sarcomere of sarcomeres end to end compose a myofibril. The functional, contractile unit of the muscle fibre. Fibrous protein strands that carry out the contraction process. Two types: thick filaments composed mainly of myosin & thin filaments Myofilaments composed mainly of actin. Thick and thin filaments slide over each other to shorten each sarcomere. Shortening of end-to-end sarcomeres shortens the entire muscle. Copyright© McGraw-Hill Education. Permission required for reproduction or display. STRUCTURAL HIERARCHY OF SKELETAL MUSCLE  LEARNING OUTCOMES By the end of this lecture you should be able to:  List the characteristic features of skeletal muscle √  Describe the structural components of a muscle fibre √  Name the major proteins in muscle fibres and state the function of each √  Describe the structures & processes involved in the stimulation & contraction of skeletal muscle fibres  Describe the stages of a muscle twitch  SKELETAL MUSCLE CONTRACTION When skeletal muscle fibre contracts:  sarcomeres shorten  H bands & I bands get smaller  Zones of overlap get larger  Z lines move closer together as thick & thin filaments slide past each other  width of A band remains constant  during shortening, dystrophin & linking proteins pull on extracellular proteins  transfers pull to extracellular tissue  SKELETAL MUSCLE CONTRACTION When skeletal muscle fibre contracts:  sliding occurs in all sarcomeres in myofibril  myofibril gets shorter  muscle fibre gets shorter  muscle gets shorter  produces tension  only contract when stimulated by a nerve  THE NERVE-MUSCLE RELATIONSHIP MOTOR NEURONS & MOTOR UNITS Somatic motor neurons  nerve cells whose cell bodies lie in brainstem & spinal cord  somatic motor fibres - axons that lead to skeletal muscle  each nerve fibre branches to supply number of muscle fibres Figure 11.6  MOTOR NEURONS & MOTOR UNITS  motor unit - one nerve fiber & all muscle fibres innervated by it  muscle fibres of one motor unit:  dispersed throughout muscle  contract in unison  produce weak contraction over wide area  able to sustain long-term contraction as motor units take turns contracting  contraction usually requires contraction of several motor units at once Figure 11.6  MOTOR NEURONS & MOTOR UNITS  average motor unit contains 200 muscle fibres  small motor units - fine degree of control  3-6 muscle fibres per neuron  eye & hand muscles  large motor units - more strength than control  powerful contractions supplied by large motor units with hundreds of fibres  gastrocnemius has ±1,000 muscle fibres per neuron  THE NEUROMUSCULAR JUNCTION  synapse - where nerve fiber meets target cell  neuromuscular junction (NMJ) - when target cell is a muscle fibre  terminal branches of nerve fibres within NMJ form synapses with muscle fibres  one nerve fibre stimulates the muscle fiber at several points within the NMJ Figure 11.7b  THE NEUROMUSCULAR JUNCTION  axon terminal - swollen end of nerve fibre  contains synaptic vesicles with acetylcholine (ACh)  synaptic cleft - gap between axon terminal & sarcolemma Figure 11.7b  THE NEUROMUSCULAR JUNCTION  nerve impulse causes synaptic vesicles to release ACh into synaptic cleft  muscle cell has multiple ACh receptors - proteins incorporated into membrane  junctional folds of sarcolemma beneath axon terminal increase surface area holding ACh receptors  lack of receptors causes weakness in myasthenia gravis  basal lamina - thin layer of collagen & glycoprotein separating Schwann cell & muscle cell from surrounding tissues  contains acetylcholinesterase (AChE) that breaks down ACh – allows muscle to relax  NEUROMUSCULAR JUNCTION [HIGH MAGNIFICATION] Photos © McGraw-Hill Education Skeletal muscle fibre [blue] Axon of motor nerve [blue] Motor end plate [blue]  ELECTRICALLY EXCITABLE CELLS  muscle fibres & neurons are electrically excitable  cell membranes exhibit voltage changes in response to stimulation  voltage (electrical potential) - difference in electrical charge from one point to another  resting membrane potential: ± −90 mV in skeletal muscle cells  maintained by sodium–potassium pump  ELECTRICALLY EXCITABLE CELLS  In an unstimulated (resting) cell:  more anions (negatively charged particles) on inside of cell membrane than outside  anions make inside of plasma membrane negatively charged by comparison to outer surface  plasma membrane is electrically polarized (charged) with a negative resting membrane potential (RMP)  there are excess sodium ions (Na+ ) in extracellular fluid (ECF)  excess potassium ions (K + ) in intracellular fluid (ICF)  ELECTRICALLY EXCITABLE CELLS Stimulated (active) muscle fibre or nerve cell  Na+ ion gates open in the plasma membrane  Na+ flows into cell down its electrochemical gradient  these cations override the negative charges in the ICF  depolarization: inside of plasma membrane becomes positive  ELECTRICALLY EXCITABLE CELLS  Stimulated (active) muscle fibre or nerve cell  Na+ gates close & K + gates open  K + moves out of cell partly repelled by positive Na+ charge & partly because of its concentration gradient  loss of positive K + ions turns membrane negative again (repolarization)  this voltage shift (depolarization & repolarization) is an action potential  ELECTRICALLY EXCITABLE CELLS  resting membrane potential (RMP) - cell not yet stimulated  action potential is a quick event seen in a stimulated excitable cell  action potential perpetuates itself down the length of cell membrane  at one point AP causes another to happen immediately in front of it  this in turn triggers another  wave of excitation is called an impulse  NEUROMUSCULAR TOXINS & PARALYSIS  toxins can interfere with synaptic function - can paralyze muscles  some pesticides contain cholinesterase inhibitors  bind to acetylcholinesterase & prevent it from degrading ACh  spastic paralysis: state of continual contraction of muscles - suffocation  NEUROMUSCULAR TOXINS & PARALYSIS Tetanus (lockjaw) - form of spastic paralysis caused by toxin Clostridium tetani  glycine in spinal cord normally inhibits motor neurons from producing unwanted muscle contractions  tetanus toxin blocks glycine release & causes overstimulation & spastic paralysis of the muscles  NEUROMUSCULAR TOXINS & PARALYSIS  flaccid paralysis - muscles are limp & cannot contract  Botulism - food poisoning caused by a neuromuscular toxin secreted by the bacterium Clostridium botulinum  blocks release of ACh causing flaccid paralysis  basis for botox injections  SKELETAL MUSCLE CONTRACTION  Four major phases of contraction and relaxation 1. Excitation  process in which nerve action potentials lead to muscle action potentials 2. Excitation-contraction coupling  events that link action potentials on sarcolemma to activation of myofilaments - preparing them to contract 3. Contraction  muscle fibre develops tension & may shorten 4. Relaxation  stimulation ends - muscle fibre relaxes & returns to its resting length  EXCITATION OF A MUSCLE FIBRE ▪ action potential arrives at synaptic terminal ▪ Acetylcholine is released ▪ permeability of membrane changes & triggers release of ACh Figure 11.8 (1, 2)  EXCITATION OF A MUSCLE FIBRE ▪ ACh molecules cross synaptic cleft & bind to ACh receptors on sarcolemma ▪ Na+ ions rushing into sarcolemma generate an action potential Figure 11.8 (3, 4) EXCITATION OF A MUSCLE FIBRE Figure 11.8 (5)  EXCITATION-CONTRACTION COUPLING ▪ action potential spreads along each T tubule Figure 11.9 (6, 7)  EXCITATION–CONTRACTION COUPLING ▪ in resting state tropomyosin strands cover active sites on thin filaments ▪ prevents cross-bridge formation ▪ Ca+ binds to & changes shape of troponin molecule ▪ troponin molecule roles tropomyosin from active sites Figure 11.9 (8, 9)  CONTRACTION CYCLE ▪ energised myosin heads bind to active sites of F-actin ▪ formation of cross-bridges ▪ contraction cycle begins Figure 11.10 (10, 11)  CONTRACTION CYCLE ▪ myosin head pivots towards M line requires energy referred to as power stroke Figure 11.10 (12, 13) MUSCLE RELAXATION Figure 11.11 (14, 15) RELAXATION Figure 11.11 (16)  RELAXATION ▪ free myosin head splits ATP into ADP & a phosphate group ▪ energy released ‘cocks’ myosin head ▪ cycle can now be repeated ▪ ATP binds to myosin head & breaks link to actin ▪ active site now exposed again ready to form new cross-bridge Figure 11.11 (17, 18)  LEARNING OUTCOMES By the end of this lecture you should be able to:  List the characteristic features of skeletal muscle √  Describe the structural components of a muscle fibre √  Name the major proteins in muscle fibres and state the function of each √  Describe the structures & processes involved in the stimulation & contraction of skeletal muscle fibres √  Describe the stages of a muscle twitch  THE LENGTH–TENSION RELATIONSHIP & MUSCLE TONE  Length-tension relationship - amount of tension generated by a muscle depends on how stretched or shortened it was before it was stimulated  if overly shortened before stimulated, a weak contraction results, as thick filaments approach Z discs  if too stretched before stimulated, a weak contraction results, as minimal overlap between thick & thin filaments results in minimal cross-bridge formation  optimum resting length produces greatest force when muscle contracts  nervous system maintains muscle tone (partial contraction) to ensure that resting muscles are near this length LENGTH-TENSION RELATIONSHIP Figure 11.12  RIGOR MORTIS  hardening of muscles & stiffening of body  starts 3-4 hours after death  deteriorating sarcoplasmic reticulum releases Ca+2  allows Ca+2 to enter cytosol  Ca+2 activates myosin-actin cross-bridging  muscle contracts, but cannot relax  muscle relaxation requires ATP - no longer produced after death  fibres remain contracted until myofilaments begin to decay  rigor mortis peaks ± 12 hours after death  diminishes over the next 48-60 hours  THRESHOLD, LATENT PERIOD & TWITCH  stimulation of muscle cause contraction - sarcomeres shorten  sarcomere shortening produces tension  more pivoting cross-bridges, more tension  single stimulation produces single contraction or twitch (lasts 7-100 millisecs)  too short to be useful so extended by repeated stimulation  sustained muscular contractions  THRESHOLD, LATENT PERIOD & TWITCH ▪ Threshold - minimum voltage necessary to generate an action potential in muscle fibre & produce contraction  Twitch - cycle of contraction & relaxation when stimulus at threshold or higher  Latent period - very brief delay between stimulus & contraction  time required for excitation, excitation-contraction coupling & tensing of elastic components of muscle (generating internal tension)  Contraction phase - time when muscle generates external tension  force generated can overcome the load & cause movement  Relaxation phase - time when tension declines to baseline  SR reabsorbs Ca2+ , myosin releases actin & tension decreases  takes longer than contraction A MUSCLE TWITCH Figure 11.13  CONTRACTION STRENGTH OF TWITCHES  even if same voltage is delivered, different stimuli cause twitches varying in strength because:  muscle starting length influences tension generation  muscle fatigue after continual use  warmer muscle enzymes work more quickly  muscle cell hydration level influences cross-bridge formation  increasing the frequency of stimulus delivery increases tension output  CONTRACTION STRENGTH OF TWITCHES  muscles must contract with variable strength for different tasks  stimulating nerves with higher voltages produces stronger contractions  higher voltages excite more nerve fibers - stimulates more motor units to contract  recruitment of multiple motor unit (MMU) - summation - process of bringing more motor units into play with stronger stimuli  weak stimuli (low voltage) recruit small units  strong stimuli recruit small & large units for powerful movements RELATIONSHIP BETWEEN STIMULUS INTENSITY (VOLTAGE) & MUSCLE TENSION Figure 11.14  CONTRACTION STRENGTH OF TWITCHES  low frequency stimuli produce identical twitches  higher frequency stimuli produce temporal (wave) summation  each new twitch ‘rides’ on previous one generating higher tension  only partial relaxation between stimuli resulting in incomplete tetanus  unnaturally high stimulus frequencies cause steady contraction called complete (fused) tetanus RELATIONSHIP BETWEEN STIMULUS FREQUENCY & MUSCLE TENSION Figure 11.15  STIMULATION OF MUSCLE  peak tension can increase with successive stimulation  if stimulation occurs straight after the relaxation phase of last twitch tension increases  this is called treppe (trep-eh)  not common in skeletal muscle  probably due to rise in Ca+ ions in sarcoplasm  STIMULATION OF MUSCLE  if a second stimulus arrives before relaxation phase has ended a second stronger contraction occurs  summation of twitches - wave summation  if muscle fibre is never allowed to relax tension will rise almost to peak tension  incomplete tetanus (tetanus = convulsive tension)  STIMULATION OF MUSCLE  if a higher stimulation frequency eliminates relaxation phase complete tetanus occurs  action potentials arrive so rapidly the sarcoplasmic reticulum cannot reclaim Ca+  as Ca+ concentration in sarcoplasm increases contraction is prolonged making it continuous  LEARNING OUTCOMES By the end of this lecture you should be able to:  List the characteristic features of skeletal muscle √  Describe the structural components of a muscle fibre √  Name the major proteins in muscle fibres and state the function of each √  Describe the structures & processes involved in the stimulation & contraction of skeletal muscle fibres √  Describe the stages of a muscle twitch √  NEXT LECTURE: INTEGUMENTARY SYSTEM