BB. 10-W-Unit1 Lect7-10 Muscle Posted Handout

8/6/2019 BB. 10-W-Unit1 Lect7-10 Muscle Posted Handout

1/93

1

Skeletal Muscle:Neuromuscular Junction

SarcomereSliding Filament Mechanism

Cross-bridge Cycle

Regulation by Ca2+

Excitation-Contraction CouplingUnit 1


2/93

2

Muscle Converts Chemical Energy To Produce

Force & MovementPerformance:Movement, Speed,Strength, & Power

HEATInternal Movement:

Blood Flow, Digestion,etc

Heart Beat


3/93

3

Figure 9.01

Figure 9-1- Muscle Types

Skeletal Cardiac Smooth


4/93

4

Muscle contraction leads to:1. Support and movement of the skeleton

(skeletal muscle)

2. Generation of pressure in hollow cavities(cardiac muscle and smooth muscle)

3. Changes in the diameter of hollow tubes(smooth muscle)


5/93

Muscle

Muscle fibers

Muscle fiber

MyofibrilSarcomere

Modified from McMahon,Muscles, Reflexes and LocomotionPrinceton University Press, 1984.

Structural Hierarchy of Skeletal Muscle

About half of the bodys mass is

composed of skeletal muscle

Most muscles linked to bones by

tendons

Skeletal muscles make up asystem of mechanical levers that

develop forces and via contraction


6/93

6

Neuronal Control of Skeletal Muscle Contraction

Motor neuron cell body receivesinhibitory and excitatory inputs

from:

1. Afferent neurons

2. Spinal cord interneurons3. Cortex via descending tracts

Motor neuron output at

synapse is ALWAYS

excitatory to the muscle

fiber.

s


7/93

7

Fig. 09.13aFigure 9-13a

ACh

ACh

ACh

ACh

ACh

1 Motor neuron innervates >1 Muscle fiber

1 Muscle fiber receives input from ONLY 1 motor neuron


8/93

8

Fig. 09.14 The Neuromuscular Junction

The synapse between a motor neuron and a muscle fiber:


9/93

9

Fig. 09.15

Figure 9-15

Neuromuscular

Junction-

Events leading

to AP in musclefiber

= end plate potential(EPP)


10/93

10

Relationship between AP in motor neuron and EPP (end plate potential)

1. EPP is always excitatory (depolarizing)

2. EPP is graded, but is always above threshold and generates APs in the

muscle membrane

3. The APs propagate along the membrane and into the T-tubules,

causing Ca2+ release from the SR and cross-bridge cycling


11/93

11

Figure 9-10 Relationship between muscle AP and muscle contraction

(Twitch)


12/93

12

Fig. 09.02

Figure 9-2

Structure of Skeletal Muscle


13/93

13

Fig. 09.03

Figure 9-3 The Sarcomere


14/93

14

THE SARCOMERE

ACTIN

Myosin


15/93

15

Fig. 09.07

Figure 9-7 Thick and Thin Filaments


16/93

16

Figure 9-6 Sliding Filament Mechanism

Contraction:Activation of force generating sites.

May or may not be associated with shortening


17/93

17

Fig. 09.05

Figure 9-5

Sliding Filament

Mechanism


18/93

18

How striatedmuscle works:The Sliding Filament Model

thickandthin filamentsinterdigitate

filaments sliderelativeto each other

filamentlengthdoesnotchange


19/93

19

From Vander, Sherman, Luciano

Human Physiology, McGraw-Hill.

Antiparallel arrangement of myosin heads pull the Z-lines

towards one another causing the sarcomere to shorten

(animation)


20/93

20

Figure 9-8

The Cross Bridge Cycle- Mechanism of Force Generation in Muscle

1. Attach

2. Power Stroke

Rate limiting step = release ofPi

3. Detachment

4. Energize


21/93

21

Figure 9-8


1. Attach

2. Power Stroke


3. Detachment

4. Energize


22/93

22

Figure 9-8


1. Attach

2. Power Stroke


3. Detach

4. Energize


23/93

23

Figure 9-8


1. Attach

2. Power Stroke


3. Detach

4. Energize


24/93


25/93

25

Fig. 09.09

Figure 9-9

Ca

2+

Activation ofCross-Bridge Cycling


26/93

26

Regulation of contraction: Ca2+, Troponin, & Tropomyosin

(Animation)


27/93

27

Figure 9-11a Sarcoplasmic Reticulum, T-Tubules and Myofibrils

Source of cytosolic Ca2+ for skeletal muscle activation is the

sarcoplasmic reticulum (SR)

Ca2+ release is stimulated by AP propagating down T-tubule membrane


28/93

28

Figure 9-11b SR, T-Tubules and Myofibrils within a skeletal muscle fiber

Ended here 9/25

S i i G i


29/93

29

Sarcoplasmic Reticulum RyRGatingfrom Germann and Stanfield,Principles of Human Physiology; Pearson, Benjain Cummings 2008

Figure 12.10

DHP = dihydropyridine

receptor = voltage sensor in

T-tubule membrane

Ryanodine receptor: Ca2+

channel in the SRmembrane. Interacts

with DHP receptor, opens

and releases Ca2+ to cytosol

resulting in contraction


30/93

30

Fig. 09.12

Figure 9-12

Excitation-Contraction

Coupling in

Skeletal Muscle

SERCA

SERCA: Ca2+ ATPase

on SR membrane thatpumps Ca2+ into SR,

thereby lowering

cytosolic [Ca2+]

resulting in relaxation


31/93

3

1

Functions of ATP in Muscle

Contraction and Relaxation1. Hydrolysis of ATP by Myosin

Provides energy for force generation and cross-bridge movement.

2. Binding of ATP to Myosin

Dissociates myosin cross-bridge from actinallowing cross-bridge cycling and preventingrigor mortis.

3. Hydrolysis of ATP by CaATPase

Provides energy to pump Ca 2+ into SR producingmuscle relaxation.


32/93

3

2

Figure 9-10 Relationship between muscle AP and muscle contraction

(Twitch)


33/93

33

Problem 1

What would happen if skeletal muscle fibers

were stimulated to contract and then during

contraction the [ATP] was decreased

significantly?


34/93

34

Muscle Contraction

The action potential propagating down the axon leads to a ___________ of theaxon terminal membrane, which leads to the opening of ________channels in the

terminal membrane and diffusion of ______________the axon terminal. This

causes release of ___________ into the synaptic cleft, which diffuses across the

cleft and binds to receptors on the_______________ of the muscle cell. Binding

leads to opening of an ion channel permeable to___________, and the diffusion of

more_______ into the cell than ________ out of the cell and therefore __________of the membrane. This __________ of the membrane causes the opening

of_____________ and firing of an ____________ in the muscle fiber membrane.

The _____________ is propagated along the muscle fiber membrane and to the

interior of the fiber via_______________, and leads to release of _________ fromthe_________________. The_______ binds to _____________causing

_______________ to shift so that __________ binding sites are revealed on

___________. The__________ bind to __________ and__________ cycling

occurs. Relaxation occurs because _________ is returned to the ___________ by

the activity of the ___________ in the ______ membrane.


35/93

3

5

What you should have learned:

Skeletal muscle fiber, myofibril andarrangement of filaments in striated muscle

Sarcomere

Thick filament/myosin Thin filament/actin, troponin, tropomyosin

Cross bridge cycle

Roles of ATP in contraction and relaxation Excitation-Contraction coupling

Events at NMJ (neuromuscular junction)


36/93


37/93

37

Mechanics of Single Fiber Contraction

Load- force exerted on muscle by the weight of anobject

Tension- force exerted on an object by a contractingmuscle

Twitch- mechanical response of a single musclefiber to a single action potential

Fi 9 16


38/93

38

Fig. 9-16

Isometric and Isotonic Contractions

Velocity of contraction = Distance shortened/time = x/t

Isometric:

Fixed Length

Isotonic:Allowed to

shortenFixed Load

x

t


39/93

39

Lengthening Contraction

(also referred to as eccentric contraction)

Load > Tension

Muscle is pulled to a longer length

Not an active process

Example- sitting down, lowering an object


40/93

40

3 Key Relationships

Load-Velocity (Force-Velocity)

Isotonic Contractions

Velocity varies with load Frequency-Tension (Force-Frequency)

Isometric Contractions

Force varies with frequency of stimulations

Length-Tension Isometric Contractions

Force varies with starting sarcomere length

i 9 17 LOAD VELOCITY RELATIONSHIP


41/93

41

Figure 9-17 LOAD-VELOCITY RELATIONSHIP


42/93

42

Figure 9-18 LOAD-VELOCITY RELATIONSHIP


43/93

43

Figure 9-19

FORCE-FREQUENCY

RELATIONSHIP

Frequency of APs in fiber membrane

1 AP/200 ms = 5 AP/sec


1 AP/75 ms = 13 AP/sec


1 AP/10 ms = 100 AP/sec


44/93

44

Figure 9-20 FORCE-FREQUENCY RELATIONSHIP

frequency = 10 AP/sec

frequency = 100 AP/sec


45/93

45

Whats the mechanism behind the

force-frequency relationship? Why isnt the twitch force maximal after a

single AP?

What change occurs with increased APfrequency that causes force generation toincrease?

What limits the maximum force that can begenerated with fused tetanus?


46/93

46

Figure 9-21 LENGTH-TENSIONRELATIONSHIP

LENGTH TENSION = Longer sarcomere lengths


47/93

47

LENGTH-TENSION

RELATIONSHIP

4. Overlap of thin filaments

interferes with myosin-actin

interactions.

Shorter Sarcomere Lengths

= Longer sarcomere lengths


48/93

48

Metabolic Pathways

similar to Figure 9-22

Figure 12.11Germannand Stanfield, Principles ofHuman Physiology, Pearson

BenjaminCummings, 2008

During skeletal muscle

contraction, the primary

metabolic pathway used to

provide ATP depends onintensity of exercise and fiber

types recruited


49/93

49

Creatine Phosphate:

First available source of ATP and rapidly depleted (8-10 sec)

Utilized at the onset of any activity

Provides time for other metabolic pathways to be turned on


50/93

50

Creatine Supplementation

Decreases endogenous creatine production Small increase in muscle creatine levels (15-20%) that maxes

out in a couple of days

Creatine stimulates protein synthesis, so increase in musclemass if supplementation + exercise compared to just exercise

Enhance performance in high intensity tasks lasting < 30seconds, but not in moderate intensity, longer durationactivities

Side effects of short term supplementation Weight gain

Muscle cramps GI difficulties

Dehydration

Heat intolerance

Effects of long term Creatine supplementation not adequatelystudied yet.


51/93

51

Oxidative Phosphorylation

P

rovides most of the ATP

for moderateintensity exercise

Occurs in the Mitochondria

Requires Oxygen Primary Fuel Sources:

Glycogen for first 5-10 minutes

Blood glucose and fatty acids for next 30 min.

Fatty Acids after35-40 minutes


52/93

52

Glycolysis Makes significant amount of the ATP during high intensity

exercise High intensity = intensity exceeding 70% of maximal ATP

breakdown rate

Glucose Pyruvic acid+ 2 ATP Lactic acid + 2 ATP

Can produce ATP

in absence of oxygen During high intensity activity, adequate blood flow and O2 delivery arelimiting factors.

Can produce large amounts of ATP when enough enzymesand substrates are available

Provides ATP for about 1.3-1.6 minutes of maximal activity Fuel Sources

Glycogen

Blood Glucose


53/93

53

Primary Energy Systems Used for SportsModified from Table 84-1, Textbook of Medical Physiology, Guyton and Hall, Elsevier Saunders, 2006

CP CP +

Glycolysis

Glycolysis Glycolysis

+ OxidativePhosph.

Oxidative

Phosph.

100 m dash 200 m dash 400 m dash 800 m dash 10,000 m

skate

Jumping Basketball 100 m swim 200 m swim Cross

countryskiing

Weight

lifting

Ice hockey

dashes

Tennis 1500 m

skate

Marathon

Diving Soccer 2000 mrowing Jogging

Football

dashes

1500 m run

400 m swim

Skeletal Muscle has 3 predominant fiber types


54/93

54

Slow fibers (Type I) have a slow myosin ATPase, and so split ATP

at a slower rate. Fatigue more slowly.

Fast fibers (Type IIa and IIb) have a fast myosin ATPase and so

split ATP at a faster rate. Fatigue more quickly.

Skeletal Muscle has 3 predominant fiber typesA whole muscle is a mix of the 3 fiber types

Type I Type IIa Type IIb


55/93

55

Oxidative fibers are specialized to use primarily oxidativephosphorylation to produce ATP.

Glycolytic fibers are specialized to use primarily glycolysis to

produce ATP

Figur

e 9-25


56/93

56

Figure 9-25


57/93

57

Muscle Fatigue

Muscle Fiber Fatigue- decline in muscletension as a result of previous contractile

activity (weakness that results from activity)

Two Types:

High Frequency

Low Frequency

It is NOT due to significant ATP depletion (why

not?)

So what does cause it?

T pes of Fatig e


58/93

58

Types ofFatigue High Frequency Fatigue

from high intensity, short duration exercise

Continuous stimulation

Onset is rapid

Recovery is rapid

Caused by increased Pi, conduction failure, pH decrease

Low Frequency Fatigue from low intensity, long duration exercise

Cyclical contractions and relaxations

Onset is slower

Recovery period is longer (replenish glycogen, replace damagedproteins)

Major contributors are probably depletion of glycogen, low blood

glucose, dehydration (electrolyte imbalances, volume depletion), and

decreased pH

High Intensity Fatigue: why does elevated P


59/93

59

High Intensity Fatigue: why does elevated Picontribute to fatigue ?

Cross bridge cycling will slow as Pi

levels increasewhy?

Hi h I t it F ti C d ti F il ?


60/93

60

High Intensity Fatigue: Conduction Failure?

Think about the T-tubular space andion changes during action potentials.

Why/how, with repeated stimulation,

could no action potentials be

produced?


61/93

61

All the muscle fibers in a single

motor unit are of the same type.

Whole muscle is a mixture of

motor units.

The relative proportion of the

3 fiber types determines

muscles maximumcontraction speed,

strength and

ability to resist fatigue.


62/93


63/93

63

Recruitment of Motor Units

Figure 12.19

Figure 11-30


64/93

64

Figure 11 30


65/93

65

Size Principle Size of motor unit relates to size of fibers and size of neurons

Small motor units small muscle fibers (ie. slow oxidative)

Small muscle fibers usually innervated by motor neuron with small cell bodiesand small diameter axons

Larger motor units

large muscle fibers (ie. fast glycolytic)

Large muscle fibers usually innervated by motor neuron with large cell bodiesand large diameter axon

Order of motor unit recruitment relates to size of motor units Large neurons harder to depolarize to threshold (need greater synaptic

input)

Small neurons activated at low input, so small fibers and small motor unitsactivated first

Large neurons activated at high input, so large fibers and large motor unitsactivated last

Good because small fibers more resistant to fatigue than large fibers

Motor Unit Size Principle


66/93

66

Motor Unit Size Principle

Figure 12.20Germannand Stanfield,

Principlesof Human

Physiology, Pearson

BenjaminCummings, 2008

Smaller motor

neurons (cell

bodies and

axons) innervatesmaller motor

units and slow

fibers and are

activated first;

so X, activatedbefore Y,

activated before

Z


67/93

67

Skeletal Muscle

Exercise (training) can change the size and strength of muscle as

well as its metabolic capacity (oxidative or glycolytic), but does

not significantly alter the speed of contraction (fast or slow

myosin).


68/93

68

Muscleisplastic!

Meaningitcan Adaptto differing work

demandsplaced onit.

Increasemuscle use:hypertrophy,

increasesarcomeresinparallel

Decreasemuscle use atrophy,decrease

musclemass,losesarcomeresinparallel

Effects of Exercise and TrainingEffects of Exercise and Training


69/93

69

Strengthtraining ( weightlifting )

-hypertrophy of muscle,all fibertypesrecruited willhypertrophy

Endurancetraining ( marathon )

- littlehypertrophy

- majorbiochemicaladaptationsin muscle

- increasecapillariespermuscle fiber


70/93

70

What about fiber type conversions?What about fiber type conversions?

- controversial, withendurancetrainingthere

isevidence of typeIIb (fastglycolytic)

switchingto typeIIa (fast oxidative)

- Hardto getgooddatainhumans


71/93

71

Type I Type IIa Type IIb


72/93

Distribution of Fiber Types


73/93

73

Distribution of Fiber TypesModified from Table 1.3, p. 45, Physiology of Sport and Exercise, 1999.

ATHLETEATHLETE GENDERGENDER MUSCLEMUSCLE %% SLOWSLOW % FAST% FAST

Sprinters Male Gastroc. 24 76

Female Gastroc. 27 73

DistanceRunners

Male Gastroc.7

9 21


Weight-

lifters

Male Gastroc. 44 56

Nonathlete Male V.Lat. 47 53



74/93

74

Predict the Adaptations to

Aerobic Training Muscle fiber type

Capillary supply

Myoglobin content

Mitochondria

Oxidative enzymes

What should you have learned?


75/93

75


Isometric, isotonic and lengthening contractions

Load-Velocity Relationship

Frequency-Tension (Force-Frequency) Relationship

Length Tension Relationship Skeletal muscle energy

metabolism (sources of ATP) Types and causes of fatigue

Fiber types- similarities and differences

Whole muscle contraction and recruitment How does muscle adapt to exercise?

Understand the problem answers


76/93

76

Smooth Muscle

Unit 1

S th M l R l


77/93

77

Smooth Muscle Roles

Surrounding a hollow organ or tube: contractiongenerates a pressure to propel contents (increase

flow)

GI Tract

Bladder

Uterus

Surrounding tubes: Contraction changes diameter to

regulate flow (increase resistance to flow) GI Tract

Blood vessels

Airways

Figure 9 33


78/93

78

Figure 9-33

Arrangement of

thick and thin filaments

in smooth muscle


79/93

79

Comparison of smooth and

skeletal muscle Maximum tension per unit cross-sectional

area is similar between smooth and skeletal

Smooth muscle also demonstrates a

Length-Tension relationship, but...

Smooth muscle can develop tension over a larger

range of muscle lengths than can skeletal

Figure 9-7 Thick and Thin Filaments


80/93

80

Fig. 09.07

g

Smooth Muscle- phosphorylation of

myosin light chain regulates

myosins binding to actin


81/93

81

Fig. 09.34

Figure 9-34 Activation of smooth muscle contraction by Ca2+

Cross Bridge Cycle in Smooth Muscle


82/93

82

Increased Ca2+-Calmodulin

Increased MLCK/MLC Phosphatase ratio

PO4

PO4 + ADP

PO4 + ADP

PO4 ADP

PO4

2. Power stroke

PO4

ATP3. Detachment4. Energize

Decreased Ca2+

-Calmodulin

Decreased MLCK/MLC Phosphatase ratio

C oss dge Cyc e S oo usc e

Other than attachment step, cycle is the same as skeletal

ATP

Smooth Muscle Contraction and


83/93

83

Relaxation Contraction: Ca2+-CM complex activates MLCK,

MLCK activity > MLC phosphatase activity, MLCphosphorylated and cross-bridge cycling occurs

Rate of ATP Utilization:

Lower than in skeletal muscle

Shortening velocity is slower than skeletal

Very fatigue resistant

Relaxation: Ca2+ is removed from the cytosol by

Ca2+ ATPase on plasma membrane

Ca2+ ATPase on SR membrane

Ca2+-Na+ exchanger on the plasma membrane

MLC phosphatase activity > MLCK activityp cross

bridge cycling stops


84/93

84

Fig. 09.35Figure 9-35

Comparison ofSmooth and Skeletal

Ca2+ Activation


85/93

85


86/93

86

Multiple Activating

Signals for Smooth

Muscle

Chemical Messengers such asHormones

Paracrine factors

Neurotransmitters

Local metabolites

These messengers may causecontraction or relaxation

(excite or inhibit).


87/93

87

Smooth muscle actionpotential depolarization

is due to Ca2+influx

Figure 9-36a Spontaneous Electrical Activity (PacemakerPotential)


88/93

88

A

B

C

A: Ca2+ dependant K+ channels close and the membrane depolarizes

B: Voltage-gated Ca2+ channels open and AP occurs, cytosolic Ca2+ rises

C: Ca2+ dependant K+ channels open and membrane hyperpolarizes

D: V-gated Ca2+ channels close and cytosolic Ca2+ decreases

D

No stable resting Vm

in pacemaker cells.


89/93

Figure


90/93

90

g

9.38

Single Unit Smooth Muscle

Characteristics

1. Connected by gap junctions

2. Synchronous activity

3. Contain pacemaker cells

4. Activity altered by inputs (ie. changing

autonomic activity) to pacemaker cells

5. Contraction can be initiated by stretch

6. Examples: GI, uterine and small diameterblood vessel smooth muscle.

Figure

9 37


91/93

91

9.37

Multiunit Smooth Muscle CharacteristicsFew or no gap junctions

1. Activity is not synchronous2. No pacemaker cells

3. Richly innervated throughout the muscle

4. Not responsive to stretch

5. Contractions often do not require APs in the membrane

6. Examples: Airway and large artery smooth muscle

Comparison of Muscle Types


92/93

92

Characteristic Skeletal SmoothThick & Thin filaments

Sarcomeres-banding

Transverse tubules

Sarcoplasmic Reticulum

Gap Junctions

Ca2+ source

Site of Ca2+ regulation

Spontaneous APs

Effect of nerve input

Effect of hormonal input

Stretch causescontraction



93/93

y

Similarities and differences between skeletal

and smooth muscle

Arrangement of thick and thin filaments, dense

bodies, length-tension relationship

Cross-bridge activation

Sources of cytosolic Ca2+ and mechanisms

regulating cytosolic [Ca2+]

Neural input to smooth muscle, spontaneousAPs, pacemaker potentials

Single unit vs. Multi unit smooth muscle

Documents

BB. 10-W-Unit1 Lect7-10 Muscle Posted Handout