Muscle plasticity

Review of skeletal muscle structure

Heirarchy:

Belly → Fascicle → Fibres (myocyte) → Myofibrils (series of sarcomeres)

• epimysium - wraps around mutiple fasciles to form the belly

• endomysium → wraps around multiple fibres to form a fascicle

Myocytes = Fibres

• peripheral nuclei and striations

Components of myofibril: interact to allow contraction

• actin

• myosin

• proteins that drive muscle contraction

Mechanical coupling

• protein-protein interactions

• depolarisation of sarcoplasmic reticulum

• release of Ca2+ stores

  • voltage sensor → Dyhydropyridine receptor (DHPR)

  • conformational change of Ca2+ channel → Ryanodine (RyR)

1. AP travels down T-tubule

2. triggers Ca2+ channels

3. Ca2+ channel opens btw myoplasm and sarcoplasmic reticulum

   • voltage sensor DHPR senses this calcium

   • RyR changes shape in response

4. Calcium transient - Ca2+ released from sarcoplasmic reticulum

5. Ca2+ release initiates cross-cycling process

Cross-bride cycle for muscle contraction

• involves excitation-contraction coupling

1. Resting state

   • myosin binding site on actin blocked by tropomyosin

2. Excitation-contraction coupling

   • Ca2+ binds to troponin

   • tropomyosin moves, revealing the myosin binding site

3. Binding

   • myosin head binds to actin → cross bridge

4. Powerstroke

   • myosin heads flex (- sarcomere shortens)

   • causes detachment of ADP+Pi

5. Detachment

   • ATP binds to myosin head, causing detachment

   • if Ca2+ still on troposin → powerstroke

   • no Ca2+ → resting state

Muscle fibre classification

every muscle has a mixture of fibre types

(patchwork arrangement)

• reverse stained images for myosin-ATPase

• Fast fibres - big and pale (high myosin-ATPase)

  • white meat (chicken) - pectoral = fast glycolytic muscle

• Slow fibres - small and dark

  • leg - dark meat = slow oxidative

• different muscle role - change in proportion of fibre types

Alternative muscle dye

SDH = succ-inate dehydrogenase

• stains mitochondria

• more blue if more mitochondria

slow oxidative - blue

• more mitochondria to drive citric acid cycle

fast glycolitic is light

Muscle fibre type distribution

• semitendinosus

• faster fibres peripherally

• central fibres = slow

• breed - genetic variation

• same distribution

• sections different sizes

  • greyhounds have greater number of type II muscles peripherally → adapted for fast burst of activity

• individual variation → strong heritability and lifestyle

• species variation

  • ambush predators → more fast fibres

  • pursuit predators → travelling long distance → more slow fibres

Muscle adaptation

Area change

• hypertrophy (NOT hyperplasia) → building muscle bulk due to fibres enlarging

Length change

• hyperplasia (more muscle fibres

• NOT hypertrophy

Satellite cells

• along surface of muscle fibres

• peripheral myocyte nuclei and satellite cells → similar appearance

• stem cell like properties → differentiate into other cell types

• important in hypertrophy

• response to injury and repair

  • muscle hypertrophy + other adaptation processes

• stimulated by IGF (insulin-like growth factor) and other growth factors

• migrate → form myotubes → fuse to existing myofibres (myocytes)

Triggers for muscle adaptation [5]

• muscle is plastic and adapts in response to triggers

1. Normal development (Growth)

2. Exercise

3. Detraining

4. Aging

5. Injury/Surgery

Normal developmental changes

• heavier → increases load → hypertrophy → increased muscle force

• taller → chronic stretch → hyperplasia (sarcomeres added to ends of muscle fibres)

• Lifestyle changes

  • need to locomote

  • runner etc → linked to exercise

Impact of Exercise on muscle summary

• increased loading/contraction → selective hypertrophy

• repeated exercise (chronic, long duration 8-24hrs), low frequency stimulation of fast muscle

  • fibre plasticity: fast → slow for endurance exercise

  • (eletrical stimulation in lab)

• chronic stretch (4wks) → hyperplasia

Detraining/Immobilisation

Fibres return to typeII

• Fibres convert to type IIa (intermediate)

• occurs x2 quickly as training

• anti-gravity (weight-bearing) muscles more at risk

• post immobilisation rehab - restore fibre type (then strength training)

Muscle memory

• first time training → first time fusion of satellite cells

• hypertrophy occurs myotube formation

• detraining occurs → decreases fibre diameter (more type IIa and I than IIb)

• nuclei still present so re-training is faster

• = muscle memory

Nutrition

• muscle will not adapt if no nutrients

Protein

• skeletal muscle mass maintained if no excessive breakdown

• need plenty of protein in diet

Glycogen

• exercise capacity linked to glycogen store

• sugars drive the cross-bridge cycling process

• glycolysis

Lipid (triglyceride)

• more in oxidative (I and IIa)

Aging

• loss of muscle function

Many reasons

1. Decreased satellite cells

• reduces hypertrophic ability

• decreased muscle size and performance

2. Decreased growth hormone

3. Denervation → muscle atrophy

4. Decreased blood supply → less nutrients, build up of waste products → function drops

5. Increased fibrous connective tissue

   • prevents efficient contraction

   • less muscle

   • influences passive and decreased contractile properties

Injury [7]

• healing is fast when inflammation is not as high

• return to pre-injury status within 10-20 dyas

• No inflammation - no TGF-beta1→ myoblast → myocyte formation

1. Inflammatory response to injury

2. Satellite cells activated by inflammation

3. Satellite cells differentiate into myoblasts

4. Myoblasts differentiate into myocytes

5. Myocytes fuse to form a myofibre

6. Persistent exposure to inflammation triggers myocytes to differentiate into myofibroblasts = fibrotic tissue

7. regulate inflammation to prevent fibrotic tissue

   Myostatin and TGF (transforming growth factor)-beta1

   • prevents → myoblast → myocyte formation

   • promote myofibroblast formation

   • myostatin inhibits macrophages

Selective hypertrophy

increased loadinf/contraction

Fast fibres respond twice as fast

Fibre type plasticity

Default → become slower with increased enndurace capacity

• unless strength training is used → leads to selective hypertrophy (lifting weights)

• training - amount of exercise (endurance) and type (strength) → weights vs supporting own body weight

Muscle length changes

Chronic stretch (tension load) (4wks) increase sarcomere length by 20%

Loads of muscles

• weight → hypertrophy

• tension → hyperplasia

• time → endurance → muscle plasticity

Muscle fibre distribution summary [3]

1. varies within and btw muscles

2. varies btw individuals (activity + genetics + nutrition + age), breeds, species

3. modulated by exercise and training