Muscle Flashcards
what is skeletal muscle responsible for?
- voluntary movement of bones that allows locomotion
- control of inspiration by contraction of diaphragm
- skeletal-muscle pump allows venous return to the heart
what is the structure of striated muscle?
- myofibres joined into fascicle bundles
- myofibres contain myofibrils which are broken down into sarcomeres
- sarcomeres contain actin and myosin myofilaments
- sarcomeres align with each other to form striated appearance
- each myosin is surrounded by 6 actin filaments
what are the different bands and lines of a sarcomere?
- Z-line
- M-line
- I-band
- A-band
- H-band
what is the Z-line?
- at end of each sarcomere for anchor point of actin
- coordinates myofilament above, below and adjacently
what is the M-line?
- anchoring point of myosin
what is the I-band?
- the sarcomere between 2 Z-lines
- appears light colour in electron microscopy due to presence of actin only
what is the A-band?
- where actin and myosin overlap for muscle contraction
- appears dark on electron microscope due to presence of both actin and myosin
what is the H-band?
- contains only myosin so appears lightly lighter than A-band
what happens to the I-band and A- band during muscle contraction?
- I-band shortens as actin is pulled across myosin
- A-band stays the same length as myosin fibres have a fixed length
how is contraction of skeletal muscle initiated?
- ACh is released from NMJ and binds to nAChRs on plasma membrane of muscle fibre, causing influx of Na+, depolarisation, and AP triggering
- depolarisation passes along sarcolemma and through T-tubules
- T-tubules form a triad with the sarcoplasmic reticulum (SR), causing depolarisation in the SR
- this depolarisation causes SR to release stored Ca2+, causing an increase in intracellular Ca2+
what is the process of cross-bridge formation and skeletal muscle contraction?
- actin and myosin are in attached state
- ATP binds to myosin head, causing it to dissociate from actin
- ATP is hydrolysed to ADP + Pi, causing conformational change of myosin
- myosin head relaxes then extends to a resting conformation, and can interact if actin further down
- myosin head binds to new actin-myosin binding site to form new cross-bridge and Pi is released to strengthen the interaction
- myosin head undergoes conformational change to pull actin over the myosin (contraction)
- ADP is released, returned to attached state until ATP binds again
how is skeletal muscle summated in its contraction?
- contraction depends on frequency of stimulation
- contraction is slower than AP, so sarcolemma is prepared for contraction before the muscle is relaxed
- increased stimulation before muscle is relaxed causes twitching, then unfused tetanus state, then fused tetanus state
what is the unfused tetanus state?
- if frequency of stimulation is increased to the muscle, muscle is continuously tense and cannot relax
what is the fused tetanus state?
- if frequency of stimulation is extremely high for the muscle, there is continuous contraction due to constant Ca2+ influx
- muscle stays contracted
what are slow oxidative muscle fibres?
Type I:
- resistant to fatigue
- use oxidative phosphorylation to generate ATP in aerobic respiration
- high in mitochondria levels
- red in colour due to high levels of myoglobin so high O2 storage
- low glycogen store
what are fast oxidative muscle fibres?
Type IIa:
- resistant to fatigue
- use oxidative phosphorylation for ATP in aerobic respiration
- highest in mitochondria levels
- red in colour due to high levels of myoglobin so high O2 storage
- abundant glycogen stores
what are fast glycolytic muscle fibres?
Type IIx/IIb:
- fatiguable but generate power quickly
- white in colour due to low myoglobin levels so low O2 store
- undergo anaerobic respiration
- highest glycogen stores for glucose to generate ATP in glycolysis
- fewer mitochondria
what is an example of a type I muscle?
Soleus
- resistant to fatigue
- controls posture when standing
- if contracting for an hour, it will still generate the same levels of force
what is an example of a type IIa muscle?
Gastrocnemius:
- generates more power when walking and jogging
- can fatigue within 6 minutes
- by an hour, it can no longer contract
- more rapid contraction and generation of higher tension
what is an example of a type IIb/IIx muscle?
biceps branchii:
- generates power strokes via anaerobic respiration
- rapid contraction and generation of force
- rapid fatigue within 2 minutes and muscle can no longer contract
what are slow muscle fibres?
- half the diameter of fast fibres
- take longer to contract after nerve stimulation
what are fast muscle fibres?
take 10 milliseconds or less to contract
how does the NMJ work>
- AP enters presynaptic terminal
- depolarisation causes Ca2+-voltage gated channels to open
- influx of Ca2+ causes fusion of vesicles with presynaptic membrane to release ACh into cleft
- ACh binds to nAChRs and opens Na+ channels
- Na+ influxes into muscle membrane, depolarising it and generating an AP
- Na+ channels close and K+ channels open to repolarise the synapse
what is the mechanism of botulinum toxin on the NM?
- endoproteinase that cleave SNARE proteins which are required for docking of vesicles during exocytosis of ACh
what symptoms does botulinum toxin cause for muscles?
- food poisoning, muscle weakness, paralysis, leading to death
1st symptoms = dry mouth and double vision
2nd symptoms = GI issues such as diarrhoea and vomiting
3rd symptoms = paralysis of limbs and repsiratory muscles
what are the clinical uses of botulinum toxin?
- treatment of strabismus (crosseyed) by injection into periocular muscles
- blepharospasm (uncontrolled eyelid movements)
- cosmetic treatments: BoTox (toxin A)
what is aerobic endurance training?
- sustained, low level exercise over long distances/periods
- training above threshold
- threshold increases as fitness increases
- stimulation of slow fibres
- conversion of IIx and IIa into more fatigue-resistant fibres, but generate less power
- no change in muscle strength
- angiogenesis
what is angiogenesis?
formation of new blood capillaries through muscle for efficient O2 delivery
- reduces diffusion distance from blood to muscle
what is anaerobic training?
- brief, high intensity excerise
- stimulation of fast fibres
- no change in no. muscle fibres or distribution
- enlargement of myofibril size by addition of new myofilaments to muscle
- causes hypertrophy
what is hypertrophy?
increased diameter of muscle fibre
what energy stores does the body rely on in the first 2 mins of excerise?
- stored energy
- anaerobic glycolysis
what are the 3 sources of energy production?
- immediate energy supply from ATP and PCr stores in muscle
- depletes within 30 seconds - glycolysis under anaerobic conditions to supply ATP
- covers next minute of exercise and becomes less efficient - oxidative phosphorylation under aerobic conditions takes over
what occurs in the immediate stage of energy release?
- muscle cells have reserves of ATP and phosphocreatine (PCr)
- ADP accumulates in the cell to drive oxidative phosphorylation and Krebs cycle
- build up of ADP, AMP and Pi stimulate metabolic pathways (oxidative phosphorylation)
- creatine is recycled into PCr in mitochondria when at rest as there is an increased O2 demand
what occurs in the anaerobic (nonoxidative) phase of energy release?
- anaerobic metabolism via glycolysis
- muscle fibres store 300-400g glycogen
at what 2 points in anaerobic glycolysis do substrates enter?
- glycogenolysis of glycogen produces glucose-1-phosphate
- glucose-1-phosphate is converted to glucose-6-phosphate
- enters glycolysis at reaction 2 - uptake of glucose from blood by GLUT4
- glucose enters glycolysis to produce pyruvate
- pyruvate is converted to lactate
why is the anaerobic state of energy release inefficient?
- 2ATP molecules per glucose
- H+ from lactate lowers cell pH and leads to muscle fatigue
what is the aerobic (oxidative) phase of energy release?
- O2 delivery to tissue is increased, stimulating oxidative phosphorylation
- process is slower but more efficient
- 30ATP per glucose
- glucose is sourced from blood following breakdown of glycogen stores in liver
- lactate is released from type IIx is converted back to pyruvate to feed oxidative phosphorylation
how are waste products used to aid extended periods of exercise?
- lactate and alanine are used by liver to generate new glucose
- lactate is released from non-exercising muscles
- body redistributes glycogen stores
- increased circulation of fatty acids which muscles can uptake
- breakdown of triacylglycerols stored in the muscle
how efficient is the muscle metabolism in aerobic conditions?
- 38ATP produced in ideal conditions via liver and kidney
- usually 30ATP during muscle contraction (lower yield)
what is central muscle fatigue?
- minor factor in trained exercise
- mind over matter
what is peripheral muscle fatigue?
- at level of muscle fibre
- production of lactate and H+ ions lowering pH of muscle cells
what is fatigue?
- inability to maintain a desired output
- decline in force and velocity of muscle shortening
what is high-frequency fatigue?
- alteration in Na+/K+ balance across membrane in type II fibres
- resting potential is changed so it is harder to trigger APs
what is low frequency fatigue?
- reduced Ca2+ release from SR
- more apparent in at low frequency stimulation in type I fibres
what is ATP depletion in fatigue?
- intense stimulation can cause large drops in ATP near sites of cross-bridge formation and ATPases
what causes lactic acid build up?
- high rates of lactate production leads to cellular acidification
what is glycogen depletion in fatigue?
- loss of an easy glucose source
what is cardiac muscle?
- specific to the heart
- cardiomyocytes are striated
- myocytes are shorter, more branched and joined by intercalated discs
- electrical coupling between adjacent myocytes by gap junctions
- AP initiated in SAN pacemaker and propagates between myocytes via gap junctions to cause contraction
what is smooth muscle?
- involved in control of organ systems: digestive, urinary and reproductive
- control blood vessel and airway diameter
- circulating hormones, ANS or inflammatory mediators control smooth muscle
- non-striated
- actin fibres join at dense bodies and thick filaments intersperse around thin ones
- large variation in AP depending on muscle type
- some cannot generate APs but respond to graded changes in Vm
what are the 2 classes of smooth muscle?
- multiunit
- nerve fibres come to each individual muscle cell
- lots of innervation - unitary
- AP stimulates one muscle cell
- gap junctions enable AP to be dispersed to other muscle cells
- enables coordinated contraction
- less innervation
what is excitation-contraction coupling in skeletal muscle?
- mechanism to increase intracellular Ca2+
- depolarisation activates L-type Ca2+ channels in T-tubule membrane
what 2 effects does excitation-contraction coupling have on skeletal muscle?
- leads to opening of L-type Ca2+ channels and influx of Ca2+ into sarcoplasm
- causes mechanical tethering between L-type Ca2+ channels in T-tubule and ryanodine receptors in the SR membrane
- ryanodine channels open and Ca2+ moves into sarcoplasm
ryanodine receptors are Ca2+ release channels
what is excitation-contraction coupling in cardiac muscle?
- cardiac T-tubules are close to one branch of SR so is called dyad
- there is no mechanical tethering between L-type Ca2+ channels in T-tubules and the ryanodine receptors in the SR
- influx of Ca2+ through L-type channels activates ryanodine receptors to open
- Ca2+ enters sarcoplasm
known as calcium induced calcium release (CICR)
what does removal of calcium from the sarcoplasm cause?
- termination of muscle contraction
what are the 3 ways in which Ca2+ is removed from the sarcoplasm?
- Plasma Membrane Calcium ATPase (PCMA)
- PCMA is an active transport pump and requires hydrolysis of ATP to pump Ca2+ out of cell - sodium/calcium exchanger (NCX)
- relies on Na+ conc gradient
- 3Na+ are transported into sarcoplasm while 1 Ca+ is transported out into extracellular space - back into SR stores via SR Ca2+ ATPase
- uses ATP hydrolysis to pump Ca2+ back into SR
- buffering proteins combine with 50Ca2+ to increase storage capacity
what is excitation-contraction coupling in smooth muscle?
- smooth muscles lack triads/dyad T-tubule and SR structures
- they use caveolae which contain voltage-gated Ca2+ channels
- peripheral SR encircles caveolae as a nearby Ca2+ store
- central SR runs through enter sarcoplasm as a general Ca2+ store
how are L-type Ca2+ channels activated in smooth muscle?
- change in membrane potential, or an ATP, leads to CICR via activation of ryanodine receptors in the SR
what is the role of Gq-coupled receptors in smooth muscle?
- they are activated and cause IP3 production and IP3 receptor stimulation in SR membrane
how is sarcomere contraction similar in skeletal and cardiac muscle?
- both contain tropomyosin which interweaves around actin
- both contains a troponin complex with can block the actin-myosin binding site
- in the absence of calcium, troponin complex prevents myosin head forming a cross-bridge with actin
what is the role of calcium and troponin in skeletal and cardiac muscle cross bridge formation?
- troponin T binds to tropomyosin, troponin C binds to calcium, troponin I lays over binding site
- increase in Ca2+ levels causes calcium to bind to TnC
- this causes conformational change in TnT, causing it to pull tropomyosin and TnI out of the binding site
- cross-bridge formation can now occur
- as Ca2+ levels decrease, original conformation returns and the binding site is blocked again
what is the mechanism of contraction in smooth muscle?
- there is no troponin in smooth muscle
- calponin and caldesmon tonically inhibit actin-myosin interaction
- stimulation of contraction involves stimulation of calmodulin by Ca2+ binding
what are the downstream effects of calmodulin during contraction of smooth muscle?
- activation of Myosin Light Chain Kinase (MLCK)
- phosphorylates MLC to cause change in myosin head angle - removes inhibitory effects of calponin and caldesmon to allow cross-bridge formation
- stop contraction by dephosphorylating MLC via MLC phosphatase (MLCP)
