11-1 chapter 11 lecture outline see powerpoint image slides for all figures and tables pre-inserted...

11-1

Chapter 11

Lecture Outline

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11-2

Muscle Tissue

• Types and characteristics of muscular tissue• Microscopic anatomy of skeletal muscle• Nerve-Muscle relationship• Behavior of skeletal muscle fibers• Behavior of whole muscles• Muscle metabolism• Cardiac and smooth muscle

11-3

Introduction to Muscle

• Movement is a fundamental characteristic of all living things

• Cells capable of shortening and converting the chemical energy of ATP into mechanical energy

• Types of muscle– skeletal, cardiac and smooth

• Physiology of skeletal muscle– basis of warm-up, strength, endurance and

fatigue

11-4

Characteristics of Muscle

• Responsiveness (excitability)– to chemical signals, stretch and electrical

changes across the plasma membrane

• Conductivity– local electrical change triggers a wave of

excitation that travels along the muscle fiber

• Contractility -- shortens when stimulated

• Extensibility -- capable of being stretched

• Elasticity -- returns to its original resting length after being stretched

11-5

Skeletal Muscle

• Voluntary striated muscle attached to bones

• Muscle fibers (myofibers) as long as 30 cm

• Exhibits alternating light and dark transverse bands or striations– reflects overlapping arrangement of

internal contractile proteins

• Under conscious control (voluntary)

11-6

Connective Tissue Elements• Attachments between muscle and bone

– endomysium, perimysium, epimysium, fascia, tendon

• Collagen is extensible and elastic– stretches slightly under tension and recoils

when released• protects muscle from injury• returns muscle to its resting length

• Elastic components– parallel components parallel muscle cells– series components joined to ends of muscle

11-7

The Muscle Fiber

11-8

Muscle Fibers

• Multiple flattened nuclei inside cell membrane– fusion of multiple myoblasts during

development– unfused satellite cells nearby can multiply to

produce a small number of new myofibers

• Sarcolemma has tunnel-like infoldings or transverse (T) tubules that penetrate the cell– carry electric current to cell interior

11-9

Muscle Fibers 2

• Sarcoplasm is filled with – myofibrils (bundles of myofilaments)– glycogen for stored energy and myoglobin

for binding oxygen

• Sarcoplasmic reticulum = smooth ER– network around each myofibril– dilated end-sacs (terminal cisternea) store

calcium– triad = T tubule and 2 terminal cisternea

11-10

Thick Filaments

• Made of 200 to 500 myosin molecules– 2 entwined polypeptides (golf clubs)

• Arranged in a bundle with heads directed outward in a spiral array around the bundled tails– central area is a bare zone with no heads

11-11

Thin Filaments• Two intertwined strands fibrous (F) actin

– globular (G) actin with an active site

• Groove holds tropomyosin molecules– each blocking 6 or 7 active sites of G actins

• One small, calcium-binding troponin molecule on each tropomyosin molecule

11-12

Elastic Filaments

• Springy proteins called titin

• Anchor each thick filament to Z disc

• Prevents overstretching of sarcomere

11-13

Regulatory and Contractile Proteins

• Myosin and actin are contractile proteins• Tropomyosin and troponin = regulatory proteins

– switch that starts and stops shortening of muscle cell– contraction activated by release of calcium into sarcoplasm

and its binding to troponin, – troponin moves tropomyosin off the actin active sites

11-14

Overlap of Thick and Thin Filaments

11-15

Striations = Organization of Filaments• Dark A bands (regions) alternating with lighter I bands (regions)

– anisotrophic (A) and isotropic (I) stand for the way these regions affect polarized light

• A band is thick filament region– lighter, central H band area

contains no thin filaments• I band is thin filament region

– bisected by Z disc protein called connectin, anchoring elastic and thin filaments

– from one Z disc (Z line) to the next is a sarcomere

11-16

Striations and Sarcomeres

11-17

Relaxed and Contracted Sarcomeres

• Muscle cells shorten because their individual sarcomeres shorten – pulling Z discs closer together– pulls on sarcolemma

• Notice neither thick nor thin filaments change length during shortening

• Their overlap changes as sarcomeres shorten

11-18

Nerve-Muscle Relationships

• Skeletal muscle must be stimulated by a nerve or it will not contract

• Cell bodies of somatic motor neurons in brainstem or spinal cord

• Axons of somatic motor neurons = somatic motor fibers– terminal branches supply one muscle fiber

• Each motor neuron and all the muscle fibers it innervates = motor unit

11-19

Motor Units• A motor neuron and the muscle

fibers it innervates– dispersed throughout the muscle– when contract together causes weak

contraction over wide area– provides ability to sustain long-term

contraction as motor units take turns resting (postural control)

• Fine control– small motor units contain as few as

20 muscle fibers per nerve fiber– eye muscles

• Strength control– gastrocnemius muscle has 1000

fibers per nerve fiber

11-20

Neuromuscular Junctions (Synapse)

• Functional connection between nerve fiber and muscle cell

• Neurotransmitter (acetylcholine/ACh) released from nerve fiber stimulates muscle cell

• Components of synapse (NMJ)– synaptic knob is swollen end of nerve fiber (contains

ACh)– junctional folds region of sarcolemma

• increases surface area for ACh receptors• contains acetylcholinesterase that breaks down ACh and

causes relaxation– synaptic cleft = tiny gap between nerve and muscle

cells– Basal lamina = thin layer of collagen and glycoprotein

over all of muscle fiber

11-21

The Neuromuscular Junction

11-22

Neuromuscular Toxins

• Pesticides (cholinesterase inhibitors) – bind to acetylcholinesterase and prevent it

from degrading ACh– spastic paralysis and possible suffocation

• Tetanus or lockjaw is spastic paralysis caused by toxin of Clostridium bacteria– blocks glycine release in the spinal cord and

causes overstimulation of the muscles

• Flaccid paralysis (limp muscles) due to curare that competes with ACh– respiratory arrest

11-23

Electrically Excitable Cells

• Plasma membrane is polarized or charged – resting membrane potential due to Na+ outside

of cell and K+ and other anions inside of cell– difference in charge across the membrane =

resting membrane potential (-90 mV cell)

• Stimulation opens ion gates in membrane– ion gates open (Na+ rushes into cell and K+

rushes out of cell)• quick up-and-down voltage shift = action potential

– spreads over cell surface as nerve signal

11-24

Muscle Contraction and Relaxation

• Four actions involved in this process– excitation = nerve action potentials lead to

action potentials in muscle fiber– excitation-contraction coupling = action

potentials on the sarcolemma activate myofilaments

– contraction = shortening of muscle fiber – relaxation = return to resting length

• Images will be used to demonstrate the steps of each of these actions

11-25

Excitation of a Muscle Fiber

11-26

Excitation (steps 1 and 2)

• Nerve signal opens voltage-gated calcium channels. Calcium stimulates exocytosis of synaptic vesicles containing ACh = ACh release into synaptic cleft.

11-27

Excitation (steps 3 and 4)

Binding of ACh to receptor proteins opens Na+ and K+ channels resulting in jump in RMP from -90mV to +75mV forming an end-plate potential (EPP).

11-28

Excitation (step 5)

Voltage change in end-plate region (EPP) opens nearby voltage-gated channels producing an action potential

11-29

Excitation-Contraction Coupling

11-30

Excitation-Contraction Coupling (steps 6 and 7)

Action potential spreading over sarcolemma enters T tubules -- voltage-gated channels open in T tubules causing calcium gates to open in SR

11-31

Excitation-Contraction Coupling (steps 8 and 9)

• Calcium released by SR binds to troponin• Troponin-tropomyosin complex changes shape

and exposes active sites on actin

11-32

Contraction (steps 10 and 11)

• Myosin ATPase in myosin head hydrolyzes an ATP molecule, activating the head and “cocking” it in an extended position

• It binds to actin active site forming a cross-bridge

11-33

Contraction (steps 12 and 13)• Power stroke =

myosin head releasesADP and phosphate as it flexes pulling the thin filament past the thick

• With the binding of more ATP, the myosin head extends to attach to a new active site– half of the heads are bound to a thin

filament at one time preventing slippage– thin and thick filaments do not become

shorter, just slide past each other (sliding filament theory)

11-34

Relaxation (steps 14 and 15)

Nerve stimulation ceases and acetylcholinesterase removes ACh from receptors. Stimulation of the muscle cell ceases.

11-35

Relaxation (step 16)

• Active transport needed to pump calcium back into SR to bind to calsequestrin

• ATP is needed for muscle relaxation as well as muscle contraction

11-36

Relaxation (steps 17 and 18)

• Loss of calcium from sarcoplasm moves troponin-tropomyosin complex over active sites– stops the production or maintenance of tension

• Muscle fiber returns to its resting length due to recoil of series-elastic components and contraction of antagonistic muscles

11-37

Rigor Mortis

• Stiffening of the body beginning 3 to 4 hours after death

• Deteriorating sarcoplasmic reticulum releases calcium

• Calcium activates myosin-actin cross-bridging and muscle contracts, but can not relax.

• Muscle relaxation requires ATP and ATP production is no longer produced after death

• Fibers remain contracted until myofilaments decay

11-38

Length-Tension Relationship

• Amount of tension generated depends on length of muscle before it was stimulated– length-tension relationship (see graph next slide)

• Overly contracted (weak contraction results)– thick filaments too close to Z discs and can’t slide

• Too stretched (weak contraction results)– little overlap of thin and thick does not allow for very

many cross bridges too form

• Optimum resting length produces greatest force when muscle contracts– central nervous system maintains optimal length

producing muscle tone or partial contraction

11-39

Length-Tension Curve

11-40

Muscle Twitch in Frog

• Threshold = voltage producing an action potential– a single brief stimulus at that

voltage produces a quick cycle of contraction and relaxation called a twitch (lasting less than 1/10 second)

• A single twitch contraction is not strong enough to do any useful work

11-41

Muscle Twitch in Frog 2

• Phases of a twitch contraction– latent period (2 msec delay)

• only internal tension is generated• no visible contraction occurs since

only elastic components are being stretched

– contraction phase• external tension develops as muscle

shortens

– relaxation phase • loss of tension and return

to resting length as calcium returns to SR

11-42

Contraction Strength of Twitches

• Threshold stimuli produces twitches• Twitches unchanged despite increased

voltage• “Muscle fiber obeys an all-or-none law”

contracting to its maximum or not at all– not a true statement since twitches vary in

strength• depending upon, Ca2+ concentration, previous stretch

of the muscle, temperature, pH and hydration

• Closer stimuli produce stronger twitches

11-43

Recruitment and Stimulus Intensity

• Stimulating the whole nerve with higher and higher voltage produces stronger contractions

• More motor units are being recruited– called multiple motor unit summation– lift a glass of milk versus a whole gallon of milk

11-44

Twitch and Treppe Contractions

• Muscle stimulation at variable frequencies– low frequency (up to 10 stimuli/sec)

• each stimulus produces an identical twitch response

– moderate frequency (between 10-20 stimuli/sec)• each twitch has time to recover but develops more

tension than the one before (treppe phenomenon)– calcium was not completely put back into SR

– heat of tissue increases myosin ATPase efficiency

11-45

Incomplete and Complete Tetanus

• Higher frequency stimulation (20-40 stimuli/second) generates gradually more strength of contraction– each stimuli arrives before last one recovers

• temporal summation or wave summation

– incomplete tetanus = sustained fluttering contractions

• Maximum frequency stimulation (40-50 stimuli/second)– muscle has no time to relax at all– twitches fuse into smooth, prolonged contraction called

complete tetanus– rarely occurs in the body

11-46

Isometric and Isotonic Contractions

• Isometric muscle contraction– develops tension without changing length– important in postural muscle function and

antagonistic muscle joint stabilization• Isotonic muscle contraction

– tension while shortening = concentric– tension while lengthening = eccentric

11-47

Muscle Contraction Phases

• Isometric and isotonic phases of lifting – tension builds though the box is not moving– muscle begins to shorten– tension maintained

11-48

ATP Sources

• All muscle contraction depends on ATP• Pathways of ATP synthesis

– anaerobic fermentation (ATP production limited)• without oxygen, produces toxic lactic acid

– aerobic respiration (more ATP produced)• requires continuous oxygen supply, produces H2O and

CO2

11-49

Immediate Energy Needs

• Short, intense exercise (100 m dash)– oxygen need is supplied by

myoglobin

• Phosphagen system– myokinase transfers Pi groups

from one ADP to another forming ATP

– creatine kinase transfers Pi groups from creatine phosphate to make ATP

• Result is power enough for 1 minute brisk walk or 6 seconds of sprinting

11-50

Short-Term Energy Needs

• Glycogen-lactic acid system takes over– produces ATP for 30-40 seconds of

maximum activity• playing basketball or running around baseball

diamonds

– muscles obtain glucose from blood and stored glycogen

11-51

Long-Term Energy Needs

• Aerobic respiration needed for prolonged exercise– Produces 36 ATPs/glucose molecule

• After 40 seconds of exercise, respiratory and cardiovascular systems must deliver enough oxygen for aerobic respiration– oxygen consumption rate increases for first 3-4

minutes and then levels off to a steady state

• Limits are set by depletion of glycogen and blood glucose, loss of fluid and electrolytes

11-52

Fatigue

• Progressive weakness from use– ATP synthesis declines as glycogen is

consumed– sodium-potassium pumps fail to maintain

membrane potential and excitability– lactic acid inhibits enzyme function– accumulation of extracellular K+

hyperpolarizes the cell– motor nerve fibers use up their acetylcholine

11-53

Endurance

• Ability to maintain high-intensity exercise for >5 minutes– determined by maximum oxygen uptake

• VO2 max is proportional to body size, peaks at age 20, is larger in trained athlete and males

– nutrient availability• carbohydrate loading used by some athletes

– packs glycogen into muscle cells– adds water at same time (2.7 g water with each

gram/glycogen)» side effects include “heaviness” feeling

11-54

Oxygen Debt• Heavy breathing after strenuous exercise

– known as excess postexercise oxygen consumption (EPOC)

– typically about 11 liters extra is consumed

• Purposes for extra oxygen– replace oxygen reserves (myoglobin, blood

hemoglobin, in air in the lungs and dissolved in plasma)

– replenishing the phosphagen system– reconverting lactic acid to glucose in kidneys and

liver– serving the elevated metabolic rate that occurs as

long as the body temperature remains elevated by exercise

11-55

Slow- and Fast-Twitch Fibers

• Slow oxidative, slow-twitch fibers– more mitochondria, myoglobin and

capillaries– adapted for aerobic respiration and

resistant to fatigue– soleus and postural muscles of the

back (100msec/twitch)

11-56

Slow and Fast-Twitch Fibers

• Fast glycolytic, fast-twitch fibers– rich in enzymes for phosphagen and

glycogen-lactic acid systems– sarcoplasmic reticulum releases calcium

quickly so contractions are quicker (7.5 msec/twitch)

– extraocular eye muscles, gastrocnemius and biceps brachii

• Proportions genetically determined

11-57

Strength and Conditioning

• Strength of contraction– muscle size and fascicle arrangement

• 3 or 4 kg / cm2 of cross-sectional area

– size of motor units and motor unit recruitment– length of muscle at start of contraction

• Resistance training (weight lifting)– stimulates cell enlargement due to synthesis of

more myofilaments

• Endurance training (aerobic exercise)– produces an increase in mitochondria, glycogen and

density of capillaries

11-58

Cardiac Muscle 1

• Thick cells shaped like a log with uneven, notched ends

• Linked to each other at intercalated discs– electrical gap junctions allow cells to stimulate their

neighbors– mechanical junctions keep the cells from pulling

apart

• Sarcoplasmic reticulum less developed but large T tubules admit Ca+2 from extracellular fluid

• Damaged cells repaired by fibrosis, not mitosis

11-59

Cardiac Muscle 2

• Autorhythmic due to pacemaker cells

• Uses aerobic respiration almost exclusively– large mitochondria make it resistant to

fatigue– very vulnerable to interruptions in oxygen

supply

11-60

Smooth Muscle• Fusiform cells with one nucleus

– 30 to 200 microns long and 5 to 10 microns wide

– no striations, sarcomeres or Z discs– thin filaments attach to dense bodies

scattered throughout sarcoplasm and on sarcolemma

– SR is scanty and has no T tubules• calcium for contraction comes from extracellular

fluid

• If present, nerve supply is autonomic– releases either ACh or norepinephrine

11-61

Types of Smooth Muscle

• Multiunit smooth muscle– largest arteries, iris, pulmonary air

passages, arrector pili muscles– terminal nerve branches synapse on

myocytes– independent contraction

11-62

Types of Smooth Muscle

• Single-unit smooth muscle– most blood vessels and viscera as circular

and longitudinal muscle layers– electrically coupled by gap junctions– large number of cells contract as a unit

11-63

Stimulation of Smooth Muscle

11-64

Stimulation of Smooth Muscle

• Involuntary and contracts without nerve stimulation– hormones, CO2, low pH, stretch, O2 deficiency– pacemaker cells in GI tract are autorhythmic

• Autonomic nerve fibers have beadlike swellings called varicosities containing synaptic vesicles– stimulates multiple myocytes at diffuse

junctions

11-65

Features of Contraction and Relaxation

• Calcium triggering contraction is extracellular– calcium channels triggered to open by voltage,

hormones, neurotransmitters or cell stretching• calcium ions bind to calmodulin• activates light-chain myokinase which activates myosin

ATPase • power stroke occurs when ATP hydrolyzed

• Thin filaments pull on intermediate filaments attached to dense bodies on the plasma membrane– shortens the entire cell in a twisting fashion

11-66

• Contraction and relaxation very slow in comparison– slow myosin ATPase enzyme and slow

pumps that remove Ca+2

• Uses 10-300 times less ATP to maintain the same tension– latch-bridge mechanism maintains tetanus

(muscle tone)• keeps arteries in state of partial contraction

(vasomotor tone)

Features of Contraction and Relaxation

11-67

Contraction of Smooth Muscle

11-68

Responses to Stretch 1

• Stretch opens mechanically-gated calcium channels causing muscle response– food entering the esophagus brings on

peristalsis

• Stress-relaxation response necessary for hollow organs that gradually fill (urinary bladder)– when stretched, tissue briefly contracts then

relaxes

11-69

• Must contract forcefully when greatly stretched– thick filaments have heads along their

entire length– no orderly filament arrangement -- no Z

discs

• Plasticity is ability to adjust tension to degree of stretch such as empty bladder is not flabby

Responses to Stretch 2

11-70

Muscular Dystrophy• Hereditary diseases - skeletal muscles

degenerate and are replaced with adipose

• Disease of males– appears as child begins to walk– rarely live past 20 years of age

• Dystrophin links actin filaments to cell membrane– leads to torn cell membranes and necrosis

• Fascioscapulohumeral MD -- facial and shoulder muscle only

11-71

Myasthenia Gravis• Autoimmune disease - antibodies attack

NMJ and bind ACh receptors in clusters– receptors removed– less and less sensitive to ACh

• drooping eyelids and double vision, difficulty swallowing, weakness of the limbs, respiratory failure

• Disease of women between 20 and 40

• Treated with cholinesterase inhibitors, thymus removal or immunosuppressive agents

11-72

Myasthenia Gravis

Drooping eyelids and weakness of muscles of eye movement