Wk 3 - CNS control of movement structure and function, skeletal muscle structure and function and muscle ageing

Question 1

Describe the general functional organisation of the nervous system:

Answer 1

-Control of the internal environment -> Coordinated with the endocrine system. Perceiving and responding to events in the internal/ external environment
-Voluntary control of movement
Integrates with spinal cord reflexes
-Assimilation of experiences necessary for memory and learning

Question 2

Draw the anatomical divisions of the nervous system

Answer 2

In CNS notes

Question 3

Describe the structure of a neuron

Answer 3

-Axon (nerve fibre) -> Carries electrical message (AP) away from the cell body. Covered by Schwann cells – forms discontinuous myelin sheath along length of axon.
-Synapse -> Contact points between axon of one neuron and dendrite of another neuron.
-The increased diameter of the axon or increased myelin sheath = greater the speed of neural transmission.

Question 4

Describe multiple sclerosis and the structure of a neuron

Answer 4

-Clinical example: multiple sclerosis -> MS is a neurological disease that destroys myelin sheath of axons – occurs due to immune attack on myelin. MS results in progressive loss of nervous system function – fatigue, muscle weakness, poor motor control, loss of balance and mental depression. Exercise training improves both functional capacity and quality of life.

Question 5

What are resting membrane potentials and what is the magnitude of the resting potentials determined by?

Answer 5

-Resting membrane potentials -> Negative charge inside cells at rest (polarised) (-5 to -100mv and -40 to -75 mv in neurons). Neurons are excitable tissue. Magnitude of the resting potentials is determined by:
1. Permeability of plasma membrane to ions
2. Difference in ion concentrations across membrane -> Na+, K+ and CI- play the most important role

-Sodium greater inside of cell, potassium greater outside of cell
-Greater diffusion of potassium outwards of cell

Question 6

Describe and draw the exchange of sodium and potassium across cell membrane (sodium-potassium pump)

Answer 6

Maintained by sodium-potassium pump. Potassium tends to diffuse out of cell. Na+/K+ pump moves 2K+ in and 2 NA+ out,
(diagram in notes on CNS)

Question 7

Describe action potentials:

Answer 7

• Occurs when a stimulus of sufficient strength depolarizes the cell -> Opens Na+ channels, and Na+ diffuses into cell (inside becomes more positive)
• Repolarization -> Return to resting membrane potential. K+ leaves the cell rapidly. Na+ channels close
• All or none law -> Once a nerve impulse is initiates, it will travel the length of the neuron

Question 8

Describe neurotransmitters and synaptic transmission:

Answer 8

Chemical messenger released from presynaptic membrane. Binds to receptor on postsynaptic membrane. Causes depolarization of postsynaptic membrane.

Question 9

Describe excitatory or inhibitory neurotransmitters:

Answer 9

• Excitatory postsynaptic potentials (EPSP) -> EPSPs can promote neural depolarization in 2 ways:
  1. Temporal summation – Rapid, repetitive excitation from a single excitatory presynaptic neuron
  2. Spatial summation – Summing EPSPs from several different presynaptic neurons
• Inhibitory post synaptic potentials (IPSP) -> Causes hyperpolarization (more negative resting membrane potentials). Neurons with a more negative membrane potential resist depolarization.
  +Neuron moves towards the threshold = EPSP > IPSPs

Question 10

What is sensory information and reflexes?

Answer 10

• Joint proprioceptors -> Free nerve endings (touch, pressure and most abundant) and Golgi type receptors (found in joint ligaments)
• Muscle proprioceptors -> Muscle spindles (responds to changes in muscle length and assist in the regulation of movement) and Golgi tendon organs
• Muscle chemoreceptors

Question 11

What is proprioception?

Answer 11

-> The motor system requires sensory information about the current internal state of the muscle and position of the limbs. Proprioception is the sense of the body’s position in space based on specialized receptors that reside in the muscles, tendons and joints. Proprioceptors are sensors that provide information about joint angle, muscle length, and provide muscle tension, which is integrated to give information about the position of the limb in space

Question 12

What is the golgi tendon organ (GTO)?

Answer 12

• Monitors force development in muscle – Prevents muscle damage during excessive force generation
• Stimulation results in reflex relation of muscle – Inhibitory neurons send inhibitory postsynaptic potentials (IPSPs) to muscle alpha motor neurons
  +Ability to voluntarily oppose GTO inhibition may be related to gains in strength with training due to increased tendon stiffness

Question 13

What are muscle chemoreceptors?

Answer 13

-> Known as ‘muscle metaboreceptors’. They are sensitive to changes in the chemical environment surrounding a muscle – H+ ions (implies a change in pH), CO2 and K+. Inform CNS about metabolic rate of muscular activity – important in regulation of cardiovascular and pulmonary responses

Question 14

Describe the brain stem (midbrain, medulla oblongata, pons)

Answer 14

• Midbrain (mesencephalon) – Connects the pons and cerebral hemispheres. Functions include: controlling responses to sight, eye movement, pupil dilation, body movement and hearing
• Medulla oblongata -> Involved in control of autonomic function, relaying signals between the brain and spinal cord and coordination of body movements
• Pons -> Involved in sleep and control of autonomic function. Relays sensory information between the cerebrum and cerebellum

Question 15

Describe the cerebrum, cerebellum and brainstem:

Answer 15

-Cerebrum (cerebral cortex) -> Organization of complex movement, storage of learned experiences and reception of sensory information
-Cerebellum -> Implicated in control of movement and integration of sensory information
-Brainstem -> Role in cardiorespiratory function, locomotion, muscle tone, posture, receiving information from special senses

Question 16

Describe the spinal cord:

Answer 16

• 45cm long, encased and protected by bony vertebral column, and attaches to brainstem
• Major conduit for two-way transmission of information from skin, joints and muscles to brain
• Contains 3 types of neurons: motor, sensory and interneuron
• ‘Spinal tuning’ refers to intrinsic neural networks within spinal cord that refine voluntary movement after receiving messages from higher brain centres

Question 17

Describe the spinal cord and control of voluntary movement:

Answer 17

-> Involves cooperation of many areas of brain along with subcortical areas. Motor cortex receives inputs from variety of brain areas including basal nuclei, cerebellum and thalamus. Spinal mechanisms results in refinement of motor control. Feedback from proprioceptors allows for further modification in motor control.

Question 18

Draw the table for sports-related traumatic brain injury (TBI)
-Physical, cognitive, emotional and sleep

Answer 18

-Table in notes for CNS

Question 19

How does exercise enhance brain health?

Answer 19

-Exercise improves brain function and reduces the risk of cognitive impairment associated with ageing
-Regular exercise can protect the brain against diseases like Alzheimer’s and certain types of brain injuries such as strokes
-How does exercise enhance brain health?
* Enhances cognition
* Stimulates formation of neurons
* Improves brain vascular function and blood flow
* Attenuates mechanisms driving depression
* Reduces peripheral factors for cognitive decline
* Inflammation, hypertension and insulin resistance

Question 20

Describe skeletal muscle:

Answer 20

-The human body contains over 600 skeletal muscles -> 40-50% of total body mass
-Functions of skeletal muscle -> Force production for locomotion and breathing. Force production for postural support. Heat production during cold stress. Acts as an endocrine organ
-Muscle actions -> Flexors (decrease joint angle), extensors (increase joint angle), attached to bones by tendons (origin end – fixed and insertion end – moves)
-Structure of skeletal muscle -> Connective tissue surrounding skeletal muscle

Question 21

What is epimysium, perimysium, endomysium, basement membrane and sarcolemma?

Answer 21

-Epimysium -> surrounds entire muscle
-Perimysium -> surrounds fascicles
-Endomysium -> surrounds muscle fibers
-Basement membrane -> just below endomysium
-Sarcolemma -> muscle cell membrane

Question 22

What is the microstructure of muscle fibers?

Answer 22

• Myofibrils – Contain contractile proteins (actin – thin filament and myosin – thick filament)
• Sarcomere – Includes Z line, M line, H zone, A band and I band
• Sarcoplasmic reticulum – Storage sites for calcium and terminal cisternae
• Transverse tubules – Extend from sarcolemma to sarcoplasmic reticulum

Question 23

What are satellite cells?

Answer 23

• Satellite cells play key role in muscle growth and repair – during muscle growth, satellite cells increase the number of nuclei in mature muscle fibres
• Myonuclear domain – volume of sarcoplasm surrounding each nucleus. Each nucleus can support a limited myonuclear domain
• More myonuclei allow for greater protein synthesis – Muscle hypertrophy – increased myonuclei and Muscle atrophy – decreased myonuceli

Question 24

What is the neuromuscular junction
(includes motor end plate and neuromuscular cleft)

Answer 24

-Neuromuscular junction –> junction between motor neuron and muscle fibre
-Motor end plate -> Pocket formed around motor neuron by sarcolemma
-Neuromuscular cleft -> Short gap between neuron and muscle fibre
-Acetylcholine (Ach) -> Ach is a NT released from the motor neuron. Causes an end plate potential (EPP). Depolarization of muscle fibre and signal for muscle contraction.
-The NMJ is potential site of fatigue but is also trainable – Increased size of NMJ, increased number of synaptic vesicles (Ach), increased number of Ach receptors on post-synaptic membrane.

Question 25

What is the sliding filament model and cross-bridge formation?

Answer 25

-Sliding filament model -> A model of muscle contraction. Muscle shortening occurs due to the movement of the actin filament over the myosin filament. Reduction in the distance between Z lines of the sarcomere. -Cross-bridge formation -> actin and myosin form to create a ‘power stroke’.

Question 26

Describe the sliding filament model movements:

Answer 26

* Thin filament with 2 chains of actin proteins in double row and twisted with a tropomyosin thread and troponin at the calcium-binding site * Thick filament shows with a myosin head and tail * The head of a myosin on the thick filament (with an ATP binding site) attaches to the actin-binding site on the thin filament

Question 27

What is energy for muscle contraction:

Answer 27

* ATP is required to muscle contraction. * Release of energy from ATP hydrolysis provides energy required for power stroke – Myosin ATPase breaks down as fibre contracts and ATP->ADP+Pi. * Sources of ATP – PC, glycolysis and oxidative phosphorylation. * Repeated contraction cycle – a single contraction cycle shortens the muscle by ~1% of resting length and some muscle can shorten up to 60% of resting length.

Question 28

What are the 4 stages of cross bridge cycling?

Answer 28

1. Energised mysoin cross bridges on the thick filaments bind to actin 2. Cross bridge binding triggers release of ATP hydrolysis products from myosin, producing angular movement 3. ATP bound to myosin, breaking link between actin and myosin -> cross bridge dissociate 4. ATP bound to myosin, is split, energizing the myosin cross bridge -ATPase -> an enzyme which determines the speed of ATP hydrolysis and resulting sarcomere shortening velocity

Question 29

Describe regulation of excitation contraction coupling (8 steps)

Answer 29

-NMJ: Excitation contraction coupling -> 1. Motor neuron’s action potential arrives at the axon terminal Depolarizes plasma membrane 2. Opening Ca2+ channels Ca2+ ions diffuse into axon terminal and Ca2+ binds to proteins 3. Synaptic vesicles release Ach 4. Ach diffuses from axon terminal to motor end plate, binding to nicotinic receptors 5. Binding of Ach opens an ion channel Na+ and K+ can pass through these channels (electrochemical gradient across plasma membrane means more Na moves in than K+ out) 6. Local depolarization of the motor end plate# 7. Muscle fibre action potential initiated 8. Propagation (end plate potential)

Question 30

Describe exercise and muscle fatigue:

Answer 30

-Muscle fatigue = a decline in muscle power output -A decline in muscle output occurs due to -> Decrease in muscle force production at the cross-bridge/ peripheral level and Changes in CNS – central fatigue. -Causes of fatigue are multifactorial -> The exact cause of muscle fatigue depends on the exercise intensity that produces fatigue

Question 31

Draw the table for the 4 categories (domain) of exercise intensity:

Answer 31

-Found in skeletal muscle notes

Question 32

Describe the mechanisms of muscle fatigue (heavy intensity 1-10 minutes)

Answer 32

* Peripheral mechanisms of fatigue during heavy, very heavy and severs exercise (1-10 min) * Possible causes of fatigue – Decreased Ca2+ release from the sarcoplasmic reticulum. Accumulation of metabolites that inhibit myofilament sensitivity to CA2+ * Key metabolites contributing to fatigue – Pi and H+ and free radicals. Pi and free radicals modify cross bridge head and reduce number of cross-bridges bound to actin. H+ ions bind to Ca2+ binding sites on troponin, preventing Ca2+ binding and contraction

Question 33

Describe the mechanisms of muscle fatigue (moderate intensity >60 mins)

Answer 33

* Mechanisms of fatigue during moderate exercise (>60min) * Possible causes of fatigue – Increased radical production and glycogen depletion * Key metabolites contributing to fatigue – Accumulation of Pi and H+ do not contribute to fatigue during moderate intensity exercise. Radical accumulation modifies cross-bridge head and reduces number of cross-bridges bound to actin. Depletion of muscle glycogen reduces TCA cycle intermediates and decreases ATP production via oxidative phosphorylation.

Question 34

What are exercise associated muscle cramps?

Answer 34

-EAMS = spasmodic, involuntary muscle contractions -> often associated with prolonged, high-intensity exercise -In some extreme conditions (e.g. prolonged exercise in a hot environment) electrolyte imbalance could cause EAMS. -EAMS likely caused by hyperactive motor neurons in the spinal cord -> High intensity exercise can alter muscle spindle and GTO function. Increased excitatory activity of muscle spindles and reduced inhibitory effect of the GTO -Strategies to alleviate EAMS -> Passive stretching and activating ion channels in the mouth/throat could send inhibitory signals to the spinal cord, and thus inhibit overactive motor neurons

Question 35

Describe the muscle actions of isotonic and isokinetic (concentric/ eccentric and isometric)

Answer 35

-Isotonic -> muscle tension remains unchanged where muscle length decreases -Isokinetic -> Muscle length decreases with constant velocity -Ranvier (1873) recognised skeletal muscle differed in colour and contractile properties -Concentric -> Muscle contracts with force greater than resistance and shortens (upwards movement) -Eccentric -> Muscle contracts with force less than resistance and lengthens (downwards movement) -Isometric -> Muscle contracts but does not change length

Question 36

What are the 3 key biochemical characteristics important to skeletal muscle fibres

Answer 36

* Oxidative capacity – quantity of mitochondria, capillaries and myoglobin in and around fibre * Types of myosin isoform expressed – 3 types that differ in activity (i.e. rate of ATP breakdown) * Abundance of contractile protein within the fibre – amount of actin and myosin * (Type of motor neuron innervation)

Question 37

What are the 3 fibre types?

Answer 37

* I: Slow twitch, slow-oxidative fibres * IIa: Intermediate fibres, fast-oxidative glycolytic fibres * IIx: Fast-twitch, fast glycolytic fibres -Most muscles have a mixed composition -Different fibres have different properties -Referred to as ‘fast’ (II) and ‘slow’ (I) twitch – Fast twitch equally sub-divided (IIa and IIx). On average 45-55% type I fibres in arm and leg muscles. Large intra-individual variation (genetics, hormones). Trend in distribution consistent across muscle groups (within individuals).

Question 38

Describe the fibre composition for distance runners, track sprinters and nonathletes:

Answer 38

-Distance runners -> 70-80% slow, 20-30% fast fibers -Track sprinters -> 25-30% slow, 70-75% fast fibers -Nonathletes -> 47-53% slow, 47-53% fast fibers

Question 39

Describe contractile proteins and their functional properties in human skeletal muscle fibers

Answer 39

* Contractile properties -> Maximal force production, speed of contraction – regulated by myosin ATPase activity, maximal power output = force x shortening velocity – high force fast fibres produce high power output. Fatigue resistance and muscle fibre efficiency – lower amount of ATP used to generate force. * Contractile properties -> Muscle contraction speed (shortening velocity) depends on the rate of cross bridge cycling which depends on the myosin ATPase isoform. Shortening results in changes to the I band not the A band.

Question 40

How are muscle fibres typed?

Answer 40

1. Contractile properties 2. Muscle biopsy – small piece of muscle removed, may not be representative of entire body and surface type II >, deep type I > II 3. Oxidative capacity – number of capillaries, mitochondria and amount of myoglobin 4. Staining for type of myosin ATPase 5. Immunohistochemical staining – selective antibody binds to unique myosin proteins and fibre types differentiated by colour difference 6. Gel electrophoresis – identify myosin isoforms specific to different fibre types

Question 41

Draw the table for characteristics of human skeletal muscle fibre types

Answer 41

Table in skeletal muscle notes

Question 42

Describe the speed of muscle activation and relaxation:

Answer 42

-Muscle twitch (contraction resulting from single stimulus) -> After stimulation- short latent period exist-corresponds to depolarisation of muscle fibre. Contraction-calcium released from SR – tension is developed due to crossbridge cycling. Relaxation-uptake of calcium into SR – crossbridge detachment. -Speed of shortening is greater in fast fibres -> SR releases Ca2+ at a faster rate. Higher ATPase activity.

Question 43

Describe force regulation in muscle:

Answer 43

-Number and types of motor units recruited -> More motor units = greater force. Fast motor units = greater force -Muscle length -> ‘Ideal’ length for force generation. Increased cross-bridge formation -Firing rate of motor neurones -> Frequency of stimulation – simple twitch, summation and tetanus -Contractile history of muscle -> Rested muscle versus muscle exposed to fatiguing exercise. Warmup exercise results in ‘postactivation potentiation’. -All muscle fibres that belong to a single motor unit are of the same fibre type -Muscle force is recruited by recruiting more motor units

Question 44

How does muscle structure relate to function and what are the Henneman size principles?

Answer 44

-Structure relates to function -> Motor neurones supplying larger faster motor units have: larger cell bodies, larger diameter axons, greater number of axonal branches, sparse afferent innervation (less spindle excitatory input) and more complex and extensive motor end plate of NMJ -Henneman size principles -> Consistent pattern of recruitment. Small -> low force (fatigue resistant) and Large -> high force (fatigue susceptible). Referred to as Henneman size principle (1974). Progressive recruitment of units, force increased in a step-wise manner. -Size principles of motor units -> 1. Slow motor units have easily excited motor neurones 2. Fast motor units have higher threshold motor neurones – harder to excite

Question 45

Describe the muscle force-velocity relationship:

Answer 45

-> At any absolute force exerted by the muscle, the speed of movement is greater in muscles with a higher percentage of fast-twitch fibres. Maximum velocity of shortening is greatest as the lowest force – true for both slow and fast fibres.

Question 46

Describe the muscle force-power relationship:

Answer 46

-> At any given velocity of movement, the peak power generated is greater in a muscle with a higher percentage of fast-twitch fibres. The peak power increases with velocity up to movement speed of 200 to 300 degrees/ second – power decreases at higher velocities because force decreases with increasing movement speed. -Whole muscle function in terms of contraction speed, power output and endurance capacity will depend on fibre composition

Question 47

Describe ageing and muscle loss:

Answer 47

* Age-related muscle loss-sarcopenia * 10% muscle mass lost between 25 to 50 years * Additional 40% lost between age 50 to 80 years * Also a loss of fast fibres and gain in slow fibres * Resistance training can delay age-related muscle loss.

Question 48

Describe diabetes and muscle loss

Answer 48

* Disease related muscle loss-cachexia * Associated with progressive loss of muscle mass * Adds to the age-related loss of muscle mass * Aerobic and resistance training are protective

Question 49

Describe cancer and muscle loss:

Answer 49

* 50% of cancer patients suffer cachexia – rapid loss of muscle mass * Results in weakness, accounts for 20% of deaths in cancer patients * Regular exercise and nutrition therapy may counteract cachexia

Question 50

Describe muscular dystrophy

Answer 50

* Hereditary defects in muscle protein * Results in loss of muscle fibres and weakness * Duchene muscular dystrophy is most common in childhood – progression varies based on specific disease type

Question 51

Describe age-related changes in muscle mass, muscle fibres and muscle quality:

Answer 51

-Strength is lost with age -> Annual decline of strength is reported to be ~3-4% in men and ~2.5-3% in women -Strength losses appear greater for lower body -> Lower body ~40% decline and upper body ~33% decline. -Muscle power lower in older group -> Power = force x velocity. With age: decreased force, velocity and power. Rate of force production is important for function e.g. falls prevention. -Muscle power declines with age -> Rate of power development and peak power are sensitive to age-related changes. Women tend to show greater age-related declines in velocity than men (in strength and velocity) -Lose muscle strength with age, greater loss in lower limbs, muscle power decreases and fall likelihood increases

Question 52

What is age related loss of muscle mass (sarcopenia/ muscle atrophy)?

Answer 52

-Age related muscle loss -> The average rate of muscle mass loss after 40 years old is approximately 8% per decade of 0.5-1% per annum until 70 years old, where it then significantly increases to ~15% per decade. Most individuals 70-80 years old possess only 60-80% of the muscle mass they had at ~30 years old -There are minimal differences in type 1 fibre atrophy in old and young people, however there are significant differences in type 2 fibre differences in young and old people (usually a decline as age increases) -Muscle fibre loss -> Total fibre numbers go down, but the proportion of Type 1 remains similar, type 2 muscle have been lost. -Muscle loss and loss of strength -> Losses in muscle strength are far greater than muscle loss.

Question 53

Describe age-related muscle quality reduction:

Answer 53

-There are 5-y percentage changes in mid-thigh subcutaneous fat (SF) and intramuscular fat (IMF) areas -Age increases fat accumulation in muscle -> More fat, less muscle within muscle. -Lose muscle mass as we age, muscle fibre atrophy (type 2), muscle fibre number reduction, more fat in and between muscle. But, losses in muscle mass don’t completely explain strength loss.

Question 54

Describe age-related neuromuscular alterations:

Answer 54

-Increases age= less motor units (in number). -What are the consequences of losing motor units? -> The loss of Mus result in muscle fibres becoming denervated. This denervation is what can cause muscle fibre atrophy and potential fibre loss. However, these are adaptive processes that act to rescue force production loss from the affected muscle fibres. -Denervation and collateral reinnervation -> A process to rescue denervated fibre. Atrophying fibres can be reinnervated by remaining MU, but this creates larger Mus. Larger MU = less efficient.

Question 55

How does denervation and collateral re-innervation alter muscle characteristics?

Answer 55

-> Increased co-expression of myosin isoforms, decreased force output and decreased velocity of contraction and hence power. Reinnervation of fibres, increases size of MU and preserves some muscle mass -Denervation isn’t to fully blame for altered muscle fatigue, other changes occur during the extraction -coupling processes -> 1.Changes to EC coupling - decreased Ca2+ release from SR 2.Changes in sarcoplasmic reticulum function - decreased Ca2+ uptake 3.Slowing of the myosin molecule - decreased intrinsic speed of shortening 4.Reduced acto-myosin cross bridges - decreased force output per muscle fibre

Question 56

Why is ageing muscle more fatigue resistant?

Answer 56

-Fatigue resistance in old age -> Older adults – less fatigable than young adults during an isometric intermittent fatiguing task of the knee extensors. There are reductions in the ability to overcome fatigue in the older population. -Motor unit number decreases with age -Tupe 2 fibres are either lost, atrophy (from less innervation) or reinnervated by type 1 motor units -More type 1-like or hybrid fibres = more fatigue resistant but less force and less quick, so more falls

Question 57

How does life-long exercise influence muscle mass function?

Answer 57

-Motor unit potentials in life-long exercisers (masters athletes) -> MU size getting larger, maybe product of reinnervation. Lifelong exercise doesn’t minimise MU increase/ inefficient -Muscle characteristics in masters athletes -> Fibres loss inevitable with age but type 1 better preserved in these master endurance athletes. Muscle deterioration not removed but not as severe. The rate of force developed – i.e. power