Health and Disease Week 10 Flashcards
What are the 3 main characteristics of skeletal muscle?
- made up of fibres
- mutlinucleate
- attached to bone
- controls posture and movement
- voluntary control
- antagonistic sets of muscle
How do the multi-nucleate muscle cells form?
fusion of muscle cells during embryonic growth
define tendon
bundles of collagen fibres that attach muscle to bone
define myofibril
bundles of actin and myosin filaments that make up muscle cells
What is the main function of the sarcoplasmic reticulum?
stores calcium in vesciles which is important to release Ca2+ ions in response to signals from the nervous system
What are the 5 main components of sarcomeres?
- thin filaments
- thick filaments
- z-lines
- H zone
- M-line/discs
What are the thin filaments composed of?
actin, troponin and tropomyosin
Which band do the thin filaments make up?
the I band
What are the thick filaments composed of?
myosin and titin
What is the function of titin?
to act as a scaffold for the sarcomere
Which band do the thick filaments make up?
the A band
What are the Z-lines?
a network of proteins that hold the thin filaments (actin) in place and together
What are the Z-lines composed of?
alpha-actinin
What is the H zone?
a light area in the centre of the A band of a sarcomere that contains only thick filaments and NOT thin actin filaments
What are M-lines/discs?
proteins that link the central regions of the thick filaments
What is the M-line composed of?
myomesin
What is the structure of each myosin molecule?
- has a light and heavy chain that are intertwined
- has a double globular head
- half the head is facing the left, and half to the right
- the area between the double head is known as the M-region
What is the structure of each actin subunit?
- each subunit has an active site than can bind to the head of a myosin molecule
- tropomyosin is wound around eahc subunit
- tropomyosin is held in place by the calcium-binding protein troponin
How do the Z-lines work?
the alpha-actinins bind and cross-link the ends of F-actin filaments from adjacent sarcomeres at the Z line
What is the interaction between actin and myosin filaments regulated by?
troponin
How many types of troponin are there? What are they?
- Troponin I -> inhibitory
- Tropnin C -> calcium binding
- Troponin T -> tropomyosin binding
What happens when calcium binds to troponin C?
causes a conformational change that moves tropomyosin aside to expose the actin binding site that binds to the myosin head
What are the 3 main steps of skeletal muscle contraction?
- resting muscle state
- activation of contraction
- breaking the cross-bridge
What are the steps of the resting muscle state?
- energised myosin is bound to ADP and Pi
- tropomyosin covers the myosin binding sites on the actin filaments and prevents interaction
What are the steps of activating contraction?
- muscle stimulated by action potentials and cytosolic calcium levels increase
- calcium binds to troponin and moves it aside exposing myosin binding sites on actin
- the energised myosin molecule and ADP bind to actin
- the cross-bridge formation causes the release of ADP and Pi and movement of the crossbridge to cause contraction
What are the steps of breaking the cross-bridge?
- ATP binds to myosin and breaks the cross-bridge
- ATP is converted to ADP and myosin returns to its energised position
define motor end plate
the region of the muscle fibre directly under the terminal portion of the axon of the neurone at the neuromuscular junction
Which two components make up the neuromuscular junction?
the motor end plate + axon terminal
How does an action potential stimulate a muscle?
- action potentials in the motor neurone depolarise the axon terminal
- this opens voltage-gated calcium ion channels
- Ca2+ ions enter the cell and trigger release of acetylcholine from vesicles
- Ach diffuses and activates nicotinic acetylcholine receptors
- this causes depolarisation of the motor end plate causing an endplate potential
What are the steps of calcium release from the sarcoplasmic reticulum?
- an action potential in the muscle is propagated
- Ca2+ is released from the lateral sac
- Ca2+ binding to troponin removes the blocking action of tropomyosin
- the cross-bridge moves
- Ca2+ is taken up
- Ca2+ removal from troponin restores tropomyosin’s blocking action
What are the 2 main types of skeletal muscle fibres?
fast twitch fibres and slow twitch fibres
What are the features of fast twitch fibres?
- contract rapidly
- get energy from glycolysis
- anaerobic
- used for explosive power such as sprinting and powerlifting
What are the features of slow twitch fibres?
- contract slower
- get energy aerobically
- used for long periods of activity such as long-distance running
- fatigue resistant
How does genetic variation affect athletic performance for some?
- alpha-actinin 3 is expressed in a subset of fast twitch muscles
- a genetic variant encodes an early stop codon and causes a truncated form of alpha-actinin 3
- causes high performance in long distance running
What are features of cardiac muscle cells?
- single, polyploid nucleus
- striated pattern
- cells electrically connected by intercalated discs
- cells have 2 types of electrical activity -> pacemarker and cardaic action potentials
- heart rate is regulated by catecholamines
What causes the nucleus in cardiac cells to be polyploid?
nucleus has undergone extra DNA replication without the cell dividing
Where are the intercalated discs located?
the Z-line of the sarcomeres that hold the actin filaments together
What are the 3 types of intercalated discs?
- interdigitating folds
- mechanical junctions
- electrical junctions
define interdigitating fold
infolds at the end of cardiac cells that increase the surface area of cell-cell connection
What are the 2 types of mechanical junctions in cardiac cells?
Adherens junctions and desmosomes
What do Adherens junctions do?
join the cell membrane to the actin filaments of the cardiomyocytes to help the transmission of contractile force between different cells
What do desmosomes do?
give strong structural support between cardiomyocytes to ensure they can withstand the contractile forces
What are the electrical junctions in cardiac muscle called?
gap junctions
What is the function of gap junctions?
they allow the transmission of ions between cells allowing depolarisation
What are gap junctions made of?
a hexamer composed of connexins provided by each cell –> hexamers are shared between cells to form a gap junction with 12 subunits connecting the cells
Are cardiac pacemaker cells initiated by nerve stimulation?
no, but can be modified by stimuli from the autonomic nervous system
How do pacemaker cells generate cardiac action potentials?
they generate their own spontaneous ones
Where are the primary pacemaker cells?
in the sinoatrial node (SAN)
What are the steps of generating a pacemaker action potential?
- phase 4: a channel called the funny channel opens and allows influx of Na+ ions, causing a GRADUAL increase in membrane potential
- phase 0: T-type calcium ion channels open and allow influx, causing a rapid depolarisation of the membrane
- phase 1: voltage-gated K+ channels open and cause rapid repolarisation and K+ ions leave the cell
- the cycle repeats
What are the steps of generating cardiac muscle cell action potentials?
Phase 4: cells at resting potential known as diastole
Phase 0: voltage-gated Na+ ion channels open due to arrival of action potential from the neighbouring cell, allowing rapid influx of Na+ ions, causing rapid depolarisation
Phase 1: rapid inactivation of Na+ channels and opening and closing of K+ channels causes a very brief efflux of K+ ions as they leave, causing a ‘notch’ on the graph
Phase 2: plateau as the membrane potential remains relatively constant as the membrane is slowly repolarising
L-type Ca2+ channels allow Ca2+ ions to enter the cell after they are activated by sodium influx in phase 0
Phase 3: rapid repolarisation as L-type Ca2+ ion channels close and voltage-gated K+ channels open
Which factors increase heart rate from the SA node?
increased plasma adrenaline, increased sympathetic nerve activity
Which factors cause a decrease in heart rate from the SA node?
increase in parasympathetic nerve activity
How does Ca2+ release during the cardiac action potential cause more Ca2+ release? (calcium induced calcium release)
- L-type calcium channels open during the cardiac action potential
- small amounts of Ca2+ enter the cell to trigger the opening of Ryanodine Receptor calcium channels in the sarcoplasmic reticulum
- Ca2+ is released from the sarcoplasmic reticulum and binds to troponin to trigger cross bridge cycling
- Ca2+ is returned back into the sarcoplasmic reticulum by the sarco/endoplasmic reticulum calcium ATPase (SERCA)
- Na+/Ca2+ exchanger removes calcium out of the cell
- the membrane is repolarised by potassium channels at the end of the action potential
How is a myocardial infarction detected?
cardiac troponins are fragmented and released into the blood when the heart muscle is damaged
What is dilated cardiomyopathy (DCM)?
a heart condition caused by the left ventricle dilating, making it harder to pump blood around
What is DCM caused by?
mutations in genes including those encoding actin, myosin, alpha-actinin, titin or troponin
What are symptoms of DCM?
shortness of breath and fatigue as the left ventricle fails
What are the differences between skeletal msucle and smooth muscle?
- smooth muscle cells are much smaller than skeletal muscle cells
- less organised actin-myosin arrangement
- contraction is regulated by calcium binding to calmodulin, NOT troponin
Where is smooth muscle found?
tubular and hollow organs such as the airways, arteries, veins, intestines, uterus etc
What does relaxation of vascular smooth muscle cause?
vasodilation, increasing blood supply to the tissues
What does contraction of vascular smooth muscle cause?
vasoconstriction, decreasing blood supply to the tissues
What is the structure of smooth muscle in the intestine?
longitudinal and circular layer
What is the structure of smooth muscle in the stomach?
3 layers:
- inner oblique layer churns food and is responsible for mechanical digestion
- circular layer form the pyloric sphincter and controls flow of stomach contents into the duodenum
- longitudinal layer moves food towards the pylorus
Which layer of the stomach is made up of smooth muscle?
muscularis externa
What are the POSSIBLE functions of smooth muscle in the trachea and bronchia?
- peristalsis for expiration
- even distribution of airflow during ventilation
- supporting airway wall
- enhancing coughing
What are the 2 types of smooth muscle?
single unit and multi unit
What are the features of single unit smooth muscle?
- made of fibres in sheets
- cells connected by gap junctions
- muscle contracts as a syncytium
What are the features of multi unit smooth muscle?
- cells act as individual units
- few or no gap junctions
- allows fine grain control
What does smooth muscle have instead of Z-lines?
dense bodies
What do dense bodies do?
hold actin thin filaments allowing them to exert force -> they are attached to the sarcolemma by intermediate filaments
What are the 2 sources of calcium ions for smooth muscle contraction?
internal calcium stores and external influx through calcium ion channels
What is the calcium binding protein in smooth muscle?
calmodulin
What are the 3 major steps of smooth muscle contraction?
- resting muscle state
- activation of contraction
- breaking the cross bridge
What are the steps of the resting muscle state?
- the dephosphorylated myosin head group is held close to the myosin filament
What are the steps of activating contraction?
- the muscle is stimulated by neurotransmitters and cytosolic calcium levels increase
- calcium binds to calmodulin
- calcium-calmodulin complex binds to myosin light chain kinase (MLCK)
- MLCK is activated
- active MLCK uses ATP to phosphorylate the myosin light chains in the myosin head group
- this causes to cross bridge to move away from the thick filament to a position where it can bind to actin
What are the steps of breaking the cross-bridge?
- myosin is dephophorylated by myosin light chain phosphatase
- when Ca2+ levels are high, activity of MLCK is greater than MLCP activity, so myosin gets phosphorylated
- now Ca2+ levels have decreased, so MLCP activity is greater than MLCK, so myosin is dephosphorylated
How is the sarcoplasmic reticulum a source of calcium ions?
- action potentials can release Ca2+ stores from the SR near the plasma membrane
- second messengers can release Ca2+ stores from the SR
How does the muscle cell get Ca2+ from extracellular sources?
influx through voltage-gated Ca2+ channels in the plasma membrane
How is smooth muscle contraction in the GI tract initiated?
- slow waves are generated by pacemaker cells called interstitial cells of Cajal
- slow waves spread to the surrounding smooth muscle cells via gap junctions
How is contraction of smooth muscle through neurones stimulated?
varicosities release neurotransmitters that cause smooth muscle cells to contract or relax
define varicosity
an axon-like swelling of autonomic neurones that form motor units in smooth muscle
What are the differences between acetylcholine receptors in skeletal muscle compared to smooth muscle?
skeletal muscle= the nicotinic receptor activated by acetylcholine is an ion channel receptor
smooth muscle= the muscarinic receptor activated by acetylcholine is a G protein-coupled receptor
What are the steps of releasing internal Ca2+ stores after GPCR activation?
- trimeric G-protein with alpha, beta and gamma subunits
- activation of the GPCR activates the alpha subunit of the G protein by GDP/GTP exchange
- this causes dissociation of the alpha subunit bound to GTP from the beta-gamma subunit
- the GTP bound alpha subunit activates phospholipase C
- phospholipase C cleaves PIP2 into IP3 and DAG
- IP3 binds to IP3 receptors in the sarcoplasmic reticulum and opens calcium ion channels
- Ca2+ ions are released from the sarcoplasmic reticulum
What are the 2 main receptors in smooth muscle?
alpha-1 adrenergic receptor and beta-adrenergic receptor
What does alpha-1 adrenergic receptor do?
mediate constriction in most vascular smooth muscle
What does beta-adrenergic receptor do in smooth muscle?
mediate dilation of vascular smooth muscle and lung airway smooth muscle
How is asthma and COPD commonly treated?
- M3 muscarinic receptors control bronchioconstriction in the airways (hypersenstitive)
- beta-adrenergic receptors control smooth muscle relaxation and bronchiodilation
- beta-adrenergic agonists are used to treat asthma and COPD
define atherosclerosis
thickening or hardening of the arteries caused by a buildup of plaque in the inner lining of an artery
