Topic 3.2: Neuromuscular system - Excitation contraction coupling

basic structure of skeletal muscle (4)

composed of bundles of muscle fibres surrounded by connective tissue

muscle fibres = muscle cells → composed of cylindrical tubes made up of stacks of sarcomeres (myofibrils)

sarcomere = individual contractile units of myofibrils

sarcomere made of thick myosin and thin actin filaments

cause of straited appearance of muscles

sarcomeres have alternating dark and light bands → stacking together creates straited appearance

myofibrils - summary (3)

occupy 80% of fibre volume

100s to 1000s of myofibrils exist in each fibre

approx 1-2 micrometers in diameter

myosin appearance

2-headed golf club → have cross bridges (myosin heads) on each end of one filament

myosin structure - purpose (2)

myosin head has binding sites for actin and ATP → thin filament is composed of actin and binds to myosin head

hinge region of myosin allows for power stroke during contraction

thin filament - structure

made of actin monomers arranged into fibres and twisted together in helical structure has contractile associated filaments (regulatory proteins) → tropomyosin and troponin

thin filament - regulatory proteins summary

troponin complexes with tropomyosin

troponin has calcium ion binding site

tropomyosin composed of string of G actin molecules

thin filament at rest vs during contraction

tropomyosin filament covers binding sites on actin monomers that bind to myosin head -> muscle cannot contract as cross bridges have nothing to attach to

troponin binding to calcium ion causes conformational change which moves tropomyosin from resting position and thus expose myosin binding sites on actin filament

muscle - Z line def

dark border that defines each sarcomere -> anchors thin actin filaments and moves closer together when muscles contract

muscle - H zone def

central region of thick myosin fibres -> contains myosin filaments only with no overlapping thin actin filaments

muscle - M zone def

thin dark line down the centre of the H zone in striated myosin fibres -> anchors thick myosin filaments

site of calcium storage within muscle fibre

sarcoplasmic reticulum

purpose of T-tubules (2)

propagate action potential towards sarcoplasmic reticulum deep inside muscle cell

facilitate rapid excitation to allow contraction to occur

tendons - summary (4)

composed of connective tissue

referred to as series elastic component

facilitates attachment of muscle to bone

highly tensile and provide a degree of stretch but some resistance that needs to be overcome before contraction can occur

tendons during muscle contraction

As muscle contracts to life a load, tension builds up in the series-elastic component

load can only be lifted after tension overcomes forces on the mass of the load

tension in muscle is the sum of….

tension caused by passive stretch of series elastic component and active muscle contraction

sliding filament theory of muscle contraction - summary

thick and thin filaments slide between each other towards the M line during muscle contraction to shorten the sarcomere rather than filaments shortening themselves

structural proteins that keep sarcomere in line during repeated contractions - list (3)

1. titin

2. nebulin

3. cytoskeletal proteins

structural proteins that keep sarcomere in line during repeated contractions - titin

provides elasticity and stabilises myosin

anchors myosin filament to Z disc

structural proteins that keep sarcomere in line during repeated contractions - nebulin

stabilises position of actin filament in sarcomere

structural proteins that keep sarcomere in line during repeated contractions - cytoskeletal proteins

anchor Z lines of sarcomeres to cell membrane to hold sarcomere in place within cell

excitation contraction coupling - def

overall process by which a muscle is excited to contract and the process of contraction

From beginning of excitation from neuromuscular junction and action potentials being generated to the end of contraction

excitation contraction coupling - release of calcium ions to end of contraction steps (6)

1. Calcium ions are released from lateral sacs of the sarcoplasmic reticulum and diffuse into the sarcoplasma

2. Calcium binds to troponin on actin filaments and tropomyosin is physically moved aside to expose cross-bridge binding sites on actin molecules

3. Myosin cross bridges attach to actin and bend -> pulls actin filaments toward M line of sarcomere

4. Calcium ions actively taken up by sarcoplasmic reticulum when there is no longer local action potential

5. Tropomyosin slips back to its blocking position over binding sites on actin when calcium is no longer bound to troponin

6. Contraction ends and actin slides back to original resting position

cross bridge cycling - steps (6)

1. Tight binding in rigor state -> myosin head remains attached to position 1 until ATP molecule binds -> cross-bridge at 45° to filament

2. ATP binds to its nucleotide binding site on myosin head and myosin dissociated from actin

3. ATPase activity of myosin hydrolyses ATP to ADP and inorganic phosphate -> both remain bound to myosin

4. Myosin head swings over and binds weakly to new actin molecule (position 2) -> cross-bridge at 90° to filament

5. Release of inorganic phosphate initiates power stroke -> myosin head rotates on its hinge which pushes associates actin filament past it (cross bridge 45° to filament)

6. End of power stroke -> myosin head releases ADP and resumes tightly bound rigor state

requirement for continued cross bridge cycling (3)

action potential is being generating

calcium is binding to troponin

ATP is cycling

implications of muscle fibre arrangement

Not all have discrete proximal and distal tendons -> fibres can arrange differentially

generally relative to axis of force generation -> muscle will insert into tendon in a way to maximise force generation for that particular muscle

basic architecture of muscle fibres (3)

• Fusiform -> fibres essentially running up and down

  • Fibre length is as close to muscle fibre length as possible

• Unipennate -> fibres insert obliquely into tendon

• Bipennate -> fibres inserting on both side of the tendon obliquely

muscle architecture and function - summary

Muscles are designed for specific functions -> muscles for fine control require different architecture than muscles for force and power output

muscle architecture and force output relation

force production is proportional to muscle CSA

Muscle A has larger cross-sectional area than muscle B -> larger CSA generally means more force because there's more fibres packing into the same space

muscle architecture and force output relation - example

Biceps brachii has fusiform architecture whilst the vastus lateralis is unipennate

vastus lateralis will have a greater CSA than the biceps brachii and thus force output capability

types of muscle actions - list (3)

• Miometric/ concentric contraction

• Isometric/ fixed end contraction

• Pliometric/ eccentric contraction

Types of muscle actions - Miometric/ concentric contraction

force developed by muscle is greater than load on muscle

shortening action occurs

Types of muscle actions - isometric/ fixed end contraction

force developed by muscle is equal to load on muscle or load is immoveable

muscle length unchanged

Types of muscle actions - pliometric/ eccentric contraction

force developed by muscle is less than load on muscle

lengthening action occur

motor unit - def

motor neuron and all the muscle fibres it controls -> an action potential in a neuron causes all muscle fibres in the motor unit to contract

all fibres in a motor neuron are the same fibre type

motor unit and muscle function relation - fine movements vs heavy work

Muscles differ based on number of fibres controlled by a motor unit

Eye muscles perform fine and delicate movements -> can have as few as one muscle fibre poer motor unit (low F:N)

Quadriceps required for heavy work -> may have hundred or thousands of muscle fibres per motor unit (high F:N)

Healthy individuals of the same size, sez and age vary in the number of motor units per muscle

motor units - methods to vary strength of contraction (2)

1. Vary number of motor units recruited at any one time

2. Vary frequency of contraction of individual motor units

skeletal muscle fibres - contractile properties

fast or slow rate of contraction/ velocity of shortening

skeletal muscle fibres - metabolic properties

identified using enzyme histochemistry

myosin ATPase activity

succinate dehydrogenase

skeletal muscle fibres - metabolic properties (myosin ATPase activity)

high: type II → subdivisions of type II denoted with A, B, C,…

low: Type I

skeletal muscle fibres - metabolic properties (succinate dehydrogenase)

for aerobic metabolism

oxidative vs glycolytic metabolism

main motor unit types - list (3)

1. fast fatigable - FF

2. fast fatigue-resistant - FR

3. slow -S

main motor unit types - histochemical profile of fibres

1. fast fatigable - fast glycolytic (FG)

2. fast fatigue-resistant - fast oxidative glycolytic (FOG)

3. slow - slow oxidative (SO)

main motor unit types - morphology

1. fast fatigable - large and high innervation ratio

2. fast fatigue-resistant

3. slow - small and low innervation ratio

main motor unit type - order of recruitment

3. fast fatigable - fast glycolytic (FG)

1. fast fatigue-resistant - fast oxidative glycolytic (FOG)

1. slow - slow oxidative (SO)

main motor unit types - twitch response

1. fast fatigable - fast and strong response

2. fast fatigue-resistant - contract and relax faster and stronger than slow but less than fast fatigable

3. slow - slow and very little force

main motor unit types - repeated twitch response

1. fast fatigable - high initial force output that fatigue quickly

2. fast fatigue-resistant - more sustainable force output than FF but still unsustainable compared to S

3. slow - sustained force output → resistant to fatigue

main motor unit types - suitability

1. fast fatigable -brief responses

2. fast fatigue-resistant - both intense efforts and prolonged work

3. slow - prolonged activity

main motor unit types - enzyme histochemistry

1. fast fatigable - type IIb fibres and type IIb MyHC -> humans don't have IIb fibres but fastest-contracting fibres are designated type IIX

2. fast fatigue-resistant - type IIa fibres and type IIa MyHC

3. slow - type I fibres and type I MyHC myosin heavy chain

isometric twitch - def

response to single electrical stimulus

optimum muscle length - def

length at which max twitch recorded

summation - def

staircase effect whereby twitch responses add together in response to repeated electrical stimulation

Related to recruitment of motor units or frequency-force relationship

Number of activated motor units contributing to the force generated by the whole muscle = determined by voltage applies to muscle

tetanus - def

muscle response following stimulation of a frequency sufficient to cause fusion

frequency-force relationship - def

plot of stimulation frequency vs isometric force response

max isometric force - def

maximum tetanic force response taken from the plateau of the frequency-force relationship

hennenman’s size principle - summary

Smaller axons will produce more depolarisation than a larger axon given the same level of excitatory input due to their small membrane area -> smallest motor units have the lowest threshold for activation and are thus first to fire

As task intensity increases -> recruit larger and faster motor units for more power output but prone to fatigue so peak power is unsustainable

Smaller motor units keep contracting -> highly oxidative metabolism and therefore resistant to fatigue

hennenman’s size principle - implication of fast motor units and fatigue

Highly oxidative units are those that are used most

Max efforts where fast motor units also recruited = cannot be sustained because of rapid depletion of glycogen

Some evidence suggests that some of the largest motor units are so inexcitable that most people cannot recruit them voluntarily