Muscles Flashcards
Outline the intermediate structures between a sarcomere and a muscle
Fascicle - bundle of muscle fibres
Muscle fibre
Myofibrils - filaments of actin/myosin arranged in myofibrils
Define myofibril
‣ Within a fibre many chains (filaments) of actin, myosin arranged in myofibrils surrounded by sarcoplasmic reticulum - i.e. multiple sarcomeres
How big is a myofibril
2 micrometres
What are some characteristics of a skeletal muscle cell
10-100 micrometres in diametre
100 - 300mm in length
Fusion of myoblasts pre birth creating long multinucleated cells unable to divide only expand. Nuclei peripheral
What is a sarcomere
The basic sturtcural unit within a myofibril
Why does striation exist?
Sarcomeres visible on the cells longitudinally due to their outline and structure
What is an A band
Myosin and some actin - myosin and the crossover area (zone of overlap)
What is the H band
- Myosin only
What is the length of the sarcomere defined by?
The Z line to Z line - the Z line being the anchoring site for actin
What is the Z line
anchoring site for actin
M line?
Myosin filaments joined together
I band
Actin filaments only
What is the name of the area with only actin filaments
I band
What is the name of the myosin only area
H zone
What is the name of the central band in a sarcomere with actin and myosin
Zone of overlap
Or the A band with both actin and myosin
Draw a sarcomere
What are 4 characteristic non sarcomere features to a skeletal muscle cell
Lots of mitochondria
Myoglobin
Sarcoplasmic reticulum
T tubules
What is the sarcoplasmic reticulum
‣ Network of vesicular elements running longitudinally around myofibril sequestering Ca by Ca/Mg dependent ATPase
How does the sarcoplasmic reticulum sequested Ca
‣ Network of vesicular elements running longitudinally around myofibril sequestering Ca by Ca/Mg dependent ATPase
What is a terminal cistern in the skeletal muscle cell
‣ Dilated end sacs of the sarcoplasmic reticulum called terminal cisterns butt against the T tubule from both sides.
What is the triad arrangement in skeletal muscle fibres
‣ A transverse tubule and the two terminal cisterns on either side of it form a triad.
What is a T tubule?
‣ These are thousands of tiny invaginations of sarcolemma at regular places on a myofibril (A-I junction)
Where do T tubules and sarcolemma generally overlap on the sarcomere
‣ These are thousands of tiny invaginations of sarcolemma at regular places on a myofibril (A-I junction)
Form a traid with 2 terminal cisterns and a T tubule
Sarcomere length relaxed
3 micrometres
Sarcomere contracted length
2.4 micrometres
Myosin structurally
◦ Myosin: (molecular motor)
‣ Large protein (thick filament) consisting of
* Long tail - 2 interwound alpha helices with a flexible hinge (S2)
* 2 globular heads (S1) connected to long tail via S2 segment - each head has 1x heavy chain that binds 1x G actin, and 2 short chains that bind ATP
How is the myosin head arranged
◦ Myosin: (molecular motor)
‣ Large protein (thick filament) consisting of
* Long tail - 2 interwound alpha helices with a flexible hinge (S2)
* 2 globular heads (S1) connected to long tail via S2 segment - each head has 1x heavy chain that binds 1x G actin, and 2 short chains that bind ATP
What happens at the M line between myosin
‣ 2x myosins fuse together at the M line via long tails forming the thick filament
* H zone contains no myosin heads.
What hapens at the H zone with myosin
There is no myosin in the H zone
How is myosin related to actin in the zone of overlap
What does a thin filament contain
‣ thin filaments - 2x chains of F actin (double stranded cord) formed from the polymerisation of G actin
* the positive is on the Z line - anchored to the Z disks
* potentiates the ATPase of myosin
What does the thin filament do with reference to actin
‣ thin filaments - 2x chains of F actin (double stranded cord) formed from the polymerisation of G actin
* the positive is on the Z line - anchored to the Z disks
* potentiates the ATPase of myosin
Where is the thin filament anchored
‣ thin filaments - 2x chains of F actin (double stranded cord) formed from the polymerisation of G actin
* the positive is on the Z line - anchored to the Z disks
* potentiates the ATPase of myosin
What is troponin
‣ Present with tropomyosin on thin filament at regular intervals (every 7 actin
monomers)
‣ Subunits
* Troponin C – calcium detecting/binds calcium
* Troponin T – binds tropomyosin
* Troponin I - inhibits myosin ATPase
‣ Binding to Calcium causes a confirmationl change in complex allowing actin to interact with myosin
What are the 3 subunits of troponin
‣ Present with tropomyosin on thin filament at regular intervals (every 7 actin
monomers)
‣ Subunits
* Troponin C – calcium detecting/binds calcium
* Troponin T – binds tropomyosin
* Troponin I - inhibits myosin ATPase
‣ Binding to Calcium causes a confirmationl change in complex allowing actin to interact with myosin
What is tropomyosin? where does it sit? What is its function
‣ 2x α-helical chains that lie between 2x chains of actin polymers → under the
influence of Troponin, it can acts to inhibit or permit myosin-actin interaction
What is titin
large elastic protein attacting myosin to the Z line
* Maintains the thick myosin filaments in the centre of the sarcomere (maintains the central A band) during contraction * Helps return the sarcomere to resting length, prevent overdistension
What are the two different types of skeletal muscle fibres
Extrafusal and intrafusal
What is the difference between intrafusal and extrafusal muscle fibres
Extrafusal - regular contract fibres supplied by alpha motor neurons
Intrafusal muscle fibres monitor length and lie parallel to extrafusal fibres. Innervated by gamma motor neurons
What si a extrafusal muscle fibre innervated by
alpha motor neuron
What is the intrafusal muscle fibre innervated by?
gamma motor neuron
If you were to subclassify extarfusal muscle fibres into 3 domains what would they be?
Fast fatiguable
Slow fatigue resistance
Fast fatigue resistant
Describe the key characteritics of fast fatiguable muscle fibres and give an example of location
e.g. hand muscles
White muscle, no myoglobin
Fast myosin ATPase
Less mitochondria
Fine precise movements
Fast twitch
Short duration of action 10msec
very fatiguable
Glycolysis energy only, minimal ATP made and consumed rapidly
What is a type 1 extrafusal muscle fibre
Slow fatigue resistnt or slow oxidative fibre
What is a type 2a extarfusla muscle fibre
fast fatigue resistant fibre, fast oxidative
What is a type 2b extrafusal muscle fibre
fast fatigauble, glycolytic
Describe the key characteritcis of slow fatigue resisant fibres and where you’d find them?
Postural muscles e.g erector spinae
Red muscle - myoglobin, lots of mitochondria, slow myosin ATPase
Strong sustained contraction, slow twitch
Sustained contraction 100msec
Not very fatiguable
Aerobic metabolism - more ATP made and less consumed
What are the characteristics of fast fatigue resistant fibres
Red muscle with myoglobin
Fine precise movements
Fast twitch
10msec contraction
Aerobic metabolism with increased mitochondria
Slow mysoin ATPase and low SR calcium pumping capacity
More fatiguable than slow fatigue resistant muscles
How does the nerve supply differ between slow tonic fibres and fast twitch fibres?
◦ Uncommon - laryngeal, extra ocular muscles
◦ Multiple nerve terminals for one nerve distributed over the whole muscle –> repeated nerve stimulation required for one muscle action potential
◦ Slow tonic contraction - non fatiguable, do not produce propogated action potentials, do not respond rapidly and require repeated stimulation before responding. Innervation by multiple grape like nerve endings rather than end plates and distirbuted over whole muscle. Therefore respond to stimulation with tonic contraction rather than a twitch response.
How is a fast twitch fibre supplied anatomically by a nerve
Single nerve, single nerve terminal –> stimulation causing action potential that propogates form the end plate
How many fibre types might a alpah motor neurone supply
May supply multiple myocytes but only 1 fibre type per nerve
What is a motor unit
- Consists of a single anterior horn α-motor neuron, its axon and all the extrafusal skeletal muscle fibres it supplies
- Considered the “functional unit of contraction” → b/c it produces the smallest amount of
muscle contraction in response to stimulation of the α-motor neuron - The number of muscle fibres in a motor unit varies - muscles for fine movement have small motor units (few fibres per motor neurone)
- Unique to skeletal muscle
- Adjacent skeletal muscle cells electrically separated by connnective tissue prohibiting depolarisation travelling between adjacent cells
What happens to an alpha motor neuron as it approaches a NMJ
Loses myelin
◦ myelinated, cell body and dendrites then long axon) to motor end plate of cell - loses myelin as it approaches a muscle fibre dividing into several terminal buttons or end feet containing acetylcholine. These fit into folds of the thickened motor end plate - one fibre ends at one endplate (no convergence)
◦ single motor nerve for all muscle fibres it innervates (motor unit) which are not necessarily next to each other to ensure uniform contraction
What is the purpose of prejunctional nicotinic receptors? Are they different?
◦ Prejunctional nAChR – Cause +ve feedback on ACh release when stimulated by ACh
Prejunctional nAChR
◦ Specialised nAChR that differs structurally and functionally cf. postjunctional nAChR
What important enzyme is contained within the synaptic cleft
◦ Contains AChE which rapidly hydrolyses ACh into choline and acetate within the
‣ junctional folds
‣ extracellular material (basal lamina)
What does acetylcholine get broken down to?
acetate and choline
How many ACh receptors per endplate
‣ 15-40 million ACh receptors per endplate
What si the trigger for the release of synaptic vesicles from the motor neuron
◦ VG-Ca2+ channel – Permit Ca2+ influx in response to motor nerve AP –> causes increased IC [Ca2+] that mobilise synaptic vesicles for ACh release (via SNAP and VAMP proteins)
Draw a nicotinic receptor
What type of recepotr is a nicotinic receptor
Ligand gated ion channel
What % of nicotinic receptors at a NMJ need to be stimulated for an action potential to occur
10%
What causes upregulation of nicotinic receptor production?
- They can be upregulated (in response to SC injury, CVA, burns, prolonged immobility, MS, GBS, prolonged NMBD exposure)
Why might someone have less nicotonic receptors at the motor end plte than usual
downregulated (in response to myasthenia gravis, AChE overdose, OP poisoning)
Where do you find nicotonic receptors on muscle cells
Junctional and extra-junctional
For extrajunctional they are outside the motor end plate and present in small numbers iunless denervation event
What is required for post junctional receptor activation
◦ Simultaneous binding of the two α subunits by an ACh each causes a brief conformational change in the receptor
How is foetal nicotnonic receptor different to adult type
‣ Foetal - has a gamma instead of a E but still contains pentameric structure
* When foetal nAChR is activated it has amore prolonged opening of ion channel causing a single quanta of ACh can elicit a muscle AP, greater release of K from muscle (contributing to hyperkalaemic response to denervation).
* Usually disappears during synaptic maturation, however when denervation occurs foetal nAChR can be upregulated in extrajunctional areas of skeletal muscle membrane
What ions flow through a nicotinic post jucntional receptor? Does this differ to prejunctional
‣ Central ion channel pore (permits transmembrane flow of Na+, Ca2+, K+)
‣ different pentarmeric structure with altered binding characteristics * Functionally Na selectivity (not Ca) and preferential blockade during high freuqency stimulation of post junctional receptor
What is the end result of nicotinic receptor stimulation at the NMJ
◦ produces a localised membrane depolarisation (or endplate potential), which can summate and trigger a skeletal muscle AP (via activation of perijunctional VG Na+ channels) if VTHRESHOLD of -50 mV is reached (RMP -90mV)
What is threshold potential
-50mV
What is a minature end plate potential
- Baseline intermittent ACh vesicle fusing with presynaptic membrane causing miniature end plate potential - this may be the cause of localised nicotinic receptors
How is a Acetylcholine synthesised
What is the enzyme implicated in synthesis of acetylcholine
What does a nerve terminal vesicle contain?
◦ Each vesicles contain – ACh (ATPase actively pumps ACh into the vesicle), ATP, Ca2+, cholesterol, phospholipids, vesiculin
Where in the nerve terminal do you find vesicles pre junctionally
Dense bar
‣ nerve terminal cytoplasm and ‣ along the presynaptic membrane flanking a “Dense bar” * (Nb. 2x vesicles line up on either side of the “dense bar” to form an “Active zone” opposite to nAChR on the MEP)
What two stores are there of ACh within the nerve cell
Nerve terminal vesicles 80%
Stationary store in nerve cytoplasm 20%
Can ACh be released without a depolarisation event?
Yes
This causes minature end plate potentials
How much ACh is in one vesicle
1500
What voltage change does a minature end plate potential cause?
0.5-1mV
How does an action potential get translated to vesicle release
AP stops at last node of Ranvier with local electrical currents produced
Voltage gated calcium channels open –> Ca influx
Calcium binds to calmodulin –> calci-calmodulin complex –> activates enzymes changing structural proteins in the vesicle and membrane
How many vesicles are released with motor nerve depolarisation
50-200 –> 60-300k ACh
How much ACh is released per depolarisation
60-300k
What is the relationship between amount of ACh release and required release for motor nerve depolarisation
10x