Muscles Flashcards
Muscle fibres comprise of several hundred ….
Myofibrils
Define syncytium
a single cell or cytoplasmic mass containing several nuclei, formed by fusion of cells or by division of nuclei
Features of a muscle fibres
Lipid droplets - fuel for respiration
Nuclei found in periphery of fibre
Lots of mito - high rate of resp
Compare cardiac muscle to skeletal muscle
Cardiomyocytes form shorter fibres than skeletal muscle fibres
Cardiac muscle not built of syncytial fibres; they consist of single cells
Cardiac muscle contains single mono/dinucleated cells with limb-like extensions that allow the cells to connect to each other via intercalated discs
Centrally located nuclei in cardiac muscle; peripheral nuclei in muscle fibres
More mitochondria/capillaries in cardiomyocytes
Describe the length-tension relationship briefly
Amount of force exerted by a sarcomere depends on the degree of overlap between the thick and thin filaments
At full stretch , few myosin heads can attach to actin so the force exerted is weak
Beyond full contraction, the ends of the thin filament get in the way of each other and thick filaments are forced against the Z lines so force is reduced
At optimal length, all myosin head have access to actin so force is maximal
Structure of the fibres in heart walls
Muscle fibres arranged in several directions to achieve spiral like formation which allows the ventricles to contract in a wringing motion
What are intercalated discs?
Connections between cardiomyocytes
Appear as dark jagged lines due to desmosomes
Skeletal muscle fibres have gap junctions
True or false
False
Features of intercalated discs
Desmosomes allow longitudinal force transfer due to their strong adherence
Low resistance gap functions allow fast transfer of APs
strong adherence between fibres
Arrangement of myosin heads in skeletal/cardiac muscle
Antiparallel all the way around the axis
Arrangement of myosin heads in smooth muscle
Antiparallel at opposite sides
Why is the arrangement of myosin heads in smooth muscles advantageous ?
Allows longer sliding distances compared to skeletal muscle
higher amount of contraction can occur
Structure of smooth muscle
Contraction shortens the smooth muscle cell to a fraction of its length while making it thicker
3D network of myosin, actin and intermediate filaments (not sarcomeres)
actin filaments held together by cytoskeletal proteins called dense bodies
Smooth muscle cell features
Mononucleated
spindle shape
( dense network of filaments with one nucleus in the middle )
Compare the three muscle types
How does striation of skeletal muscle occur
Intermediate filaments such as desmin link Z lines laterally and myofibrils longitudinally
Z lines are laterally linked by
Desmin intermediate filaments
What proteins is mainly responsible for preventing overstretch in muscles ?
Titin
Role of myofibril cytoskeleton
Composed of mainly desmin fibres
Links myofibrils to each other
links synctycia to the basement membrane and into the surrounding connective tissue at the periphery
this allows force of contraction ti be transmitted both longitudinally and laterally
What is the endomysium ?
Connects to BM
Loose connective tissue with mixture of delicate/strong fibres that surrounds each muscle fibre
What is the perimysium ?
Mixed connective tissue , some dense, some loose, that groups muscle fibres into fascicles
where most nerves and blood vessels are found
What is the fascia ?
Dense layer of connective tissue that covers the muscle
What is the epimysium
Relatively loose connective tissue between the fascia and muscle
Identify the endomysium, a muscle fibre, the perimysium, the epimysium, a fascicle and the fascia
perimysium surrounds the fascicle
Complete the sentences:
Within muscle fibres, sarcomeres are arranged into a striated pattern by 1 _____ _____ which also transfer some of the force onto the 2 ________ , which surround the muscle fibres.
muscle fibres are bundled into 3______ which are surrounded by 4_______
the muscles are packed by 5 _____
1 intermediate filaments
2 endomysium
3 fascicles
4 perimysia
5 fascia
Which structures within a muscle are visible by naked eye ?
Fascicles can be seen as stripes
What are motor end plates
Where a motor neurone synapses with a muscle fibre
1 synapse per muscle fibre
Can AP be generated between muscle fibres?
No, AP can only be generated by motor end plates ; there are no gap junctions between muscle fibres
What is proprioception?
Sesnors in muscle fibres for stretch and speed of movement work in association with sensory neurones to allow your body to sense movement, action, and location
What is a motor unit ?
Refers to the motor neurone and the several hundred muscle fibres it attaches to
each motor neurone synapses with the same muscle fibre type
What is the size principle
The idea that type 1 fibre motor units are recruited first
if more force is required , type 2 motor units recruited
What is the difference between different fibre types ?
The isoform of myosin present
Describe structure of NMJ
Only present in skeletal muscles not cardiac muscle
State events that occur during chemical transition at a NMJ
- AP arrive at presynaptic bouton
- depolarisation of presynaptic membrane = voltage gated Ca2+ channels open
- calcium-mediated exocytosis of ACh into synaptic cleft
- ACh interacts with nAChR on sarcolemma
- Conformational change of nAChR ; influx of Na+ into muscle cell ; effluent of K+ Via nAChR ; Receptor Generated Potentials (RGPs) formed
- If RGPs exceed threshold , AP is generated; this AP is called an End Plate Potential (EPP)
- EPP propagated down muscle ; release of Ca2+ Into cytosol from SR ; muscle contracts
Adaptations of muscles that require fine muscle control
1:1 ratio of motor neurone to muscle fibre
Explain Ca2+ regulated release of ACh
AP arrives at axon terminal
terminal membrane depolarises
voltage gated Ca2+ open
Ca2+ diffuse into presynaptic bouton down conc grad
this causes exocytosis of secretory vesicles of ACh
How is the capacity for detection of ACh release at the motor end plate enhanced?
Many more nAChR proteins present in sarcolemma than ACh molecules release by a single AP
What type of receptor are nAChR receptors ?
Ionotropic
How many NMJ does each myocyte have ?
One
one presynaptic AP leads to one post-synaptic AP
describe how the neurones recover after an AP is initiated
- enzymes found in the synaptic cleft break down the neurotransmitter
- acetyl cholinesterase AChE hydrolyses ACh
- ACh→ acetic acid + choline
- these products diffuse across synaptic cleft back to presynaptic knob where they are recombined to from the neurotransmitter again
- this requires ATP
- this causes the neurotransmitters to no longer be complementary to receptor sites so the neurotransmitter is removed from nAChR in postsynaptic membrane
- NAChR therefore close
- Na+/K+ pumps work to restore resting potential
What is myasthenia gravis
Autoimmune disease of NMJ
autoantibodies against nicotine AChR = trouble with initiating muscle contractions
How is MG treated
inhibition of AChE via drugs ; prolong time ACh is present in cleft ; increase chances of binding to receptors and causing AP
What is quantal exocytosis
Small quanta (packets ) of ACh are released at rest as voltage-gated Ca2+ channels are inefficient
this causes a small membrane depolarisation called miniature EPP (mepp)
What happens inside a myocyte after muscle contraction occurs ?
Ca2+ are removed from cytosol and returned to the SR by ATP-Ca2+ pumps
How does an ACh binding to receptors of the postsynaptic membrane cause muscle contraction
ACh binds to nAChR = epp = volatge gated Na+ channels = depolarisation to threshold = AP generated
AP travels down T-tubules to SR
AP communicates ryanodie receptor
Ca2+ released by SR via voltage gated Ca2+ channels
muscle contraction
compare type 1 and type 2 fibres in terms of :
contraction time
size of motor unit
resistance to fatigue
max duration of use
force produced
mitochondrial density
capillary density
glycolytic capacity
myosin heavy chain human gene
Function of muscle spindles
Innervated by γ motor neurons ; provide info about length changes of muscle
Function of golgi tendon organs
Provide information about the strength of a muscles contraction
What are satellite cells?
Myoblasts that remain in muscle fibres to act asa stem cell reserve in case damage to myonuclei/muscle fibre occurs
Adaptation of skeletal muscles to exercise
Endurance training = Increased mito
Resistance training = muscle hypertrophy = more myofibrils within fibres
How do satellite cells replace fibres ?
Cell fusion to syncytium , myofibril synthesis and maturation
How much blood is expelled from heart every heart beat
Around 70% in a healthy person
Two main features of heart
Constant contraction
Synchronous muscle activation in ventricles
Name the 2 ways to increase function of heart
Inotripy - increased force of contraction = higher SV
chonotropy = increased frequency of contraction = increased HR
Difference between AP in skeletal muscle and cardiac muscle
Duration of cardiac AP is much longer
shorter AP in skeletal muscle allows more control over its contraction
How is cardiac muscle adapted to achieve synchronous contractions of the heart
longer AP to avoid tetanus in cardiac muscle
(tetanus is prolonged contraction of a muscle caused by rapidly repeated stimuli - you want cardiac muscle to contract with same short duration and power each time)
Longer AP achieved by plateau in AP due to influx of L-type Ca2+ channels (L for long-opening) to delay repolarisation
this allows twitch contraction of the muscle
muscle force in a single myocyte regulated is regulated by …
Frequency of action potentials
summation - no time for muscle to relax before new contraction so prolonged muscle contraction
Muscle paralysis occurs when ….
No action potentials are initiated in the muscle
How is neuromuscular blockade useful?
Prevent muscle contractions
Maintain muscle relaxation/paralysis without the need of deep general anaesthesia
surgery (inc. cosmetic )
What are the 4 ways to prevent neuromuscular transmission ?
- Prevent ACh synthesis by inhibiting choline uptake - no clinical use , slow effect and slow to reverse
- prevent exocytosis of ACh e.g botulinum toxin prevents vesicles from fusing with membrane
- block receptors e.g nicotinic receptor antagonists
- increase reuptake/inactivation of AChE
Botox - clinical uses
- Treat cervical dystopia (neuromuscular movement disorder involving head and neck)
- treat blepharospasm (involuntary eye muscle contractions )
- treat primary auxiliary hyperhidrosis (excessive sweating )
Explain how non-depolarising agents work
include details about :
Onset ; Duration ; mechanism of action ; is block preceded by stimulation of muscles?
Non-depolarising agents work by competing for the receptor binding sites on nAChR; this is called competitive antagonism
longer duration ~ 30 mins
relatively fast onset of effect ~ 3-5 mins
Block is not preceded by stimulation of muscles
During block high freq stimulation causes tetanus with slightly onset duration of twitch (called tetanic fade)
Agonism vs antagonism
Agonism = activates receptor
Antagonism = deactivates receptor
Anticholinesterases can be used to ….
Reverse neuromuscular blockade due to action of antagonists
Explain how depolarising agents work
include details of:
Mechanism of action : onset ; duration ; use ; is its blocking effect preceded by muscle stimulation?
work by leaving the nAChR permanently open ; they mimic shape of ACh or nicotine (which both fit receptor sites on nAChR)
new APs cannot be formed as overwhelms voltage gated Na+ channels ;
rapid onset <1min ;
short duration ~ 5 min
ideal for quick procedures e.g intubation , ECT(electro convulsive therapy) and dislocation
Block preceded by muscle twitches
What happens upon high freq stimulation of non-depolarising block
Tetanus with duration only slightly longer than a twitch
called tetanus fade
What happens upon high freq stimulation of depolarising block
How can you antagonise a non-depolarising block ?
Using agents that depolarise the sarcolemma
drugs that increase ACh release e.g adrenaline / 4-aminopyridine
anticholinestersases (AChE inhibitors )
name 3 common nACh-R antagonist/non-depolarising blockers
atracurium
vecuronium
gallamine
name 2 nACh-R agonist/depolarising blockers
suxamethonium
dexamethonium
name 2 common ACh-esterase inhibitor (“anticholinesterase”)
physiostigmine
neostigmine
What is Ca induced Ca release (CICR) ?
L-type Ca2+ channels are very close to ryanodine receptors on SR
Ca2+ influx during cardiac AP results in Ca2+ release by SR
small increase in [Ca2+]i
Ca2+ then re-sequestered by SR via Ca2+ATPase pump and then expelled from cell by Na+/Ca2+ exchange
difference between calcium handling apparatus in cardiac vs skeletal muscle
skeletal - thin t-tubules, thick SR, triads ( each t-tubule connects with 2 SR membranes) ; cardiac - thick t-tubules, thin SR, diads ( each t-tubule connects with 1 SR membrane)
What is the effect of increasing the diastolic length of the cardiac myocyte
Increases sensitivity of myocyte to Ca2+ = more powerful heart contraction
What does inotrope mean
Agent that alters the force of muscle contraction
How do positive cardiac inotropes work
E.g caffeine
cause more Ca2+ release from channels of the SR
How do negative inotropes work?
how do they help reduce angina/blood pressure
Block L-type Ca2+ channels
Reduced contraction = lower energy demand and blood ejected at lower force
Cardiac muscle needs ATP for
The myosin heads to detach and reset it forward
Energy sources of cardiac muscle
Mostly fat then glucose then lactate,glycolysis and ketones
Describe cardiac muscle mitochondria
They have continuous reticulum
2 distinct population :
- interfibrillar - provide ATP for muscle contraction
- subsarcolemmal - provide ATP for ATP-dependant processes in the AP
