Muscle Lectures-Lec03 Lowe2

8/13/2019 Muscle Lectures-Lec03 Lowe2

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Dawn Lowe, PhD

Associate Professor

Program in Physical Therapy and Rehabilitation Science

University of [email protected]

MUSCLE

Bioc/Phsl/BMEN 5444

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Muscle Fiber Types

Development and Growth lecture

Final slide, review articles available online

Skeletal muscle has the capacity to regenerate after

injury

What about cardiac muscle?


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Skeletal Muscle FiberPhenotypes

Classification of fiber types Biochemistry

Physiology

Morphology

Plasticity

Motor unit phenotype

Motor Unit

Definition : onemotor neuron andall of the fibers thatit innervates

Fibers within amotor unit are thesame type

10s to 1000s offibers per motorunit


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Motor units originate in the anterior horn

of the spinal cord: These cells determine

muscle fiber types

When does this

occur duringdevelopment?

Skeletal Muscle FiberPhenotypes

Classification of fiber types Biochemistry

Physiology

Morphology

Plasticity

Motor unit phenotype


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Schemes for classification of fiber types

I. Types I, IIA, and IIB

Brooke and Kaiser

Based on myosin ATPase reactivity patterns

Histochemically determined from cross-section of

frozen muscles

Stain for myosin ATPase after preincubation at

different pH Acid preincub at pH 4.3 I dark; IIA and IIB light

Acid preincub at pH 4.6 I dark; IIB intermediate; IIA light

Basic preincub at pH 10 IIA and IIB dark; I light

Fiber types based on myosin ATPasereactivity patterns


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Burke, inHandbook of Physiology, Section 1, Vol. II; p325, 1981

Myosin ATPase reactivity patterns

- Cat soleus muscle

- Acid preincubation

@ pH 4.65

- single fiber type

observed

Burke, inHandbook of Physiology, Section 1, Vol. II; p325, 1981

Myosin ATPase reactivity patterns

-Cat gastrocnemius

muscle

- Acid preincubation

@ pH 4.65

- 3 fiber types

observed

-Somewhat subjective


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Pette & Staron,Rev. Physiol. Biochem., Pharmacol. 116; 1, 1990

Fiber types based on

myosin heavy chain (MHC) isoforms

MHC IIa

MHC IIx

MHC IIb

MHC I

Kraemer et al., inExercise and Sports Sciences Reviews 24;p363, 1996

- Comparison of

myosin ATPase

activity with MHC

isoforms

- Hybrids or co-

expression

(pH 4.6)


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Different myosin heavy chain (MHC) isoforms confer

the biochemical differences

In post-natal skeletal muscle there are 4 MHC isoforms

I, IIa, IIb, and IIx

These isoforms >80% homologous (i.e., their amino acid

sequences are < 20% different)

Fiber Types : MHC Isoforms

*

*

*

***

*

Reggiani et al.,News Physiological Sci. 15; 26, 2000

Regions where diversity among MHC isoforms tend to cluster*


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MHC diversity between and within muscles



Based on myosin

II. Types SO, FOG, and FG

Based on contractile speed and patterns of metabolic

enzymes

SO (slow twitch, oxidative), FOG (fast twitch, oxidativeand glycolytic), and FG (fast twitch, glycolytic)

Peter and co-workers


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What happens when an action potential is successful?

Twitch

(1 actionpotential ~ 1

nerve impulse)

Twitch Contractile Properties

Force parameter: peak

twitch tension (Pt)

Velocity parameters:

contraction time (CT)

relaxation time (RT)

one-half relaxation

time (1/2 RT)

peak rate of force

development (+dP/dt)

peak rate of force

decline (-dP/dt)


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What happens when multiple action potentials

are successful?

Tetanus

fusion of twitches

higher force

Muscle twitch summation

Rapid stimuli initiatetwitches before theprevious twitchcompletely relaxes. Ifgiven fast enough, forcewill be generated in asmooth pattern and willreach maximal force. Thatis, twitches will fuse into a

tetanus. Rates of force

development and decline(relaxation) ~ speed ofcontraction

5

50

75

100


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Burke &

Edgerton,Ex.

Sport Sci. Rev. 3:

31, 1975

Fiber types based on contractile speed

and metabolic enzymes

FG FOG SO

*

Burke &

Edgerton,Ex.

Sport Sci. Rev. 3:

31, 1975


and metabolic enzymes

FG FOG SO

How is ATP

generated?

G=glycolytic (non-

O2 requiring)

O=oxidative

(requires O2 and

mitochondria)


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Based on myosin


Based on contractile speed andpatterns of metabolic

enzymes

Mitochondria content (metabolic machinery to make

ATP, buts requires oxygen)



Based on myosin


Based on contractile speed and patterns of metabolicenzymes

III. Types SR, FR, FF

Burke

Based on contractile speed and fatigability


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Burke &

Edgerton,Ex.

Sport Sci. Rev. 3:

31, 1975


and fatigability

FF FR SR

*

Burke,Handbook of Physiology, Section 1, Vol. II; p325, 1981


and fatigability

fatigue-resistant


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Fiber type description should be

based on what is measured!

Fatigue or

Fatigue-resistant

Fast or Slow

Myosin

Metabolic

capacity

More characteristics of

fiber types

Relationships between classification systems


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Bottinelli et al.,J. Electromyog. Kinesiol. 9; 87, 1999

Physiology

~ 4x difference

between I and IIB

Bottinelli et al.,J. Physiol. 437; 655, 1991

Physiology

fast

slow


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Developing Fast muscles Slow muscles / Heart

Gene Family muscles (type II fibers) (type I fibers) Eye

MHC MHCemb MHC2A MHC1 / MHC /slow MHCexoc

MHCneo MHC2X MHC (atrial)

MHC2B

MLC1 MLC1emb MLC1f MLC1sa

(essential) MLC1f MLC3f MLC1sb

MLC2 MLC2f MLC2f MLC2s

(regulatory) MLC2a (atrial)

MHC and myosin light chains (MLC) expressed

in striated muscle

Bottinelli et al.,J. Physiol. 437; 655, 1991

Physiology

100% 1f

100% 3f


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Physiology


Physiology

~ 10x difference

between I and IIB


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Biochemistry

Glycolytic enzyme

Oxidative

enzyme

(Krebs cycle)

Morphology

Differences in the sarcoplasmic reticulum: Fast has

More highly developed SR

More Ca2+ ATPase protein

Different isoform of Ca2+ ATPase protein (SERCA1 vs.

SERCA2A)

Other Ca2+ handling proteins: Fast has

2x more calsequestrin

200x more parvalbumin

Therefore, Fast has faster Ca2+ uptake


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Result of having differences in the SR and Ca2+

handling proteins Fast has faster relaxation

Fast-twitch Fast-twitch Slow-twitch

Burke,Handbook of Physiology, Section 1, Vol. II; p325, 1981

Morphology

Crosses, Type I

Filled circles, Type IIA

Open circles, Type IIB

Handout

pH 10


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Morphology - MTJ

Red vs. White Muscle (~#4)

Morphology

1. High mitochondria content

2. High capillary density (bloodflow)

3. High [myoglobin]

4. High [cytochrome]


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Salmons & Vrbova,J. Physiol. 210; 535, 1969

Electrical stimulation studies:

fast to slow

Fast muscle

stimulated at 10

Hz (slow

frequency) for 41

days

Salmons & Vrbova,J. Physiol. 210; 535, 1969

Electrical stimulation studies:fast to slow


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Control of phenotypic expression is

through the motor neuron

Today, taken as fact

More contemporary issue: How does neural

activity control muscle genes? And what other

factors contribute to the control?

How does neural activity control muscle genes?

Schiaffino et al,Physiol. 22; 269, 2007

NFAT is a nerve activity sensor


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Summary of fiber types

Additional table provided in handouts

Additional references

Moss, R.L., G.M. Diffee, & M.L. Greaser. Contractile properties ofskeletal muscle fibers in relation to myofibrillar protein isoforms.Rev.

Physiol. Biochem., Pharmacol. 126; 1-63, 1995.

Schiaffino, S. M. Sandri, & M. Murgia. Activity-Dependent SignalingPathways Controlling Muscle Diversity and Plasticity.Physiol. 22;269-278, 2007.

Schiaffino, S.M. & C. Reggiani. Fiber Types in Mammalian Skeletal

Muscles.Physiol. Rev. 91; 1447-1531, 2011.

Westerblad, H., J.D. Bruton, & A. Katz. Skeletal muscle: Energy

metabolism, fiber types, fatigue and adaptability.Exp. Cell Res. 316;

3093-3099, 2010.


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Properties of Skeletal Muscle Motor Unit Types

Type II Fast (glycolytic) Type I Slow (oxidative)

Morphological Properties

Muscles: Muscles:

Fewer, larger motor units per muscle More, smaller motor units per muscleLarge motor neurons Small motor neurons

Fibers: Fibers:Large diameter Small diameterLarge, complex motor endplate Small, simple motor endplateHighly developed SR Poorly developed SRFew mitochondria Many mitochondriaThin Z discs Thick Z discsSmall amount of collagen Large amount of collagenComplex MTJ Simpler MTJ

Contractile/Physiological Properties

Large motor unit tetanic tension Small motor unit tetanic tensionShort twitch contraction time (fast twitch) Long twitch contraction time (slow twitch)

High myosin ATPase activity Low myosin ATPase activityShort relaxation time Long relaxation time

High rate & capacity for Ca++

uptake by SR Low rate & capacity for Ca++

uptake by SRLarge peak power output Small peak power outputLarge Vmax Small VmaxFast axonal conduction velocity Slow axonal conduction velocityHigh stimulus frequency to elicit peak tension Low stimulus frequency to elicit peak tensionLow sensitivity to recruitment High sensitivity to recruitment

Metabolic Properties of Muscle Fibers

Few mitochondria Many mitochondriaFew capillaries; Low capillary: fiber ratio Many capillaries; High capillary: fiber ratioLow myoglobin concentration High myoglobin concentrationLow cytochrome content High cytochrome contentLow activities of Krebs Cycle enzymes High activities of Krebs Cycle enzymesLow activities of enzymes of beta oxidation High activities of enzymes of beta oxidationHigh creatine kinase activity Low creatine kinase activityHigh myokinase activity Low myokinase activityHigh activities of glycolytic/glycogenolytic enzymes Low activities of glycolytic/glycogenolytic enzymesHigh LDH activity; LDH-5 dominant Low LDH activity; LDH-1 dominantFew lipid droplets Many lipid droplets

Low RNA content High RNA contentLow resting energy expenditure High resting energy expenditure

Fatigability

Contractile machinery rapidly fatigued Contractile machinery resistant to fatigueHigh susceptibility to neuromuscular fatigue Low susceptibility to neuromuscular fatigue

Muscle Lectures-Lec03 Lowe2

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