Lecture 9 - Skeletal muscle neurophysiology I

Question 1

Control of skeletal muscle

Answer 1

voluntary

Question 2

what does skeletal muscle act on

Answer 2

acts on the skeleton and the body has this muscle so that it can move and interact with the environment

Question 3

thin and thick filaments of skeletal muscle cause a what

Answer 3

a striation pattern

Question 4

Movements of skeletal muscle

Answer 4

Skeletal muscle exerts force on the skeleton to move you limbs and two of the most simple movements that skeletal muscle controls is flexion and extension

Question 5

Flexion

Answer 5

Flexion = reducing the angle between two bonds, involves activation of flexor muscles and relaxation of extensor muscles

Question 6

Extension

Answer 6

Extension = making the angle larger between two bones, going further apart, involves the activation/contraction of extensor muscle and the relaxation of flexor muscles

Question 7

Origin and insertion

Answer 7

Proximal insertion that attached to the bone is called the origin and the distal end that attaches to bone is called the insertion

Question 8

tendons

Answer 8

Tendons connect you skeletal muscle to you skeleton and the tendons allow for muscles to exert force on the skeleton

Question 9

Skeletal muscle fibre anatomy

Answer 9

Group of muscle fibres that are bundled together is called a fascicles/fasciculus

Within each fascicle are muscle fibres which is a muscle cell and it is multinucleate and they have myofibrils

Actin and myosin filaments are bundled together in groups called myofibrils. Myofibrils are long filaments that run parallel to each other to form muscle fibres. Myofibrils are made up of repeating subunits called sarcomeres.

Fibers are extremely small but can be extremely long

Question 10

Myofibrils are made up of

Answer 10

repeating subunits called sarcomeres

Question 11

Sarcomere is an

Answer 11

an individual contractile unit. The myofilaments are arranged in a regular pattern along the length of the muscle fibre in repeated units known as sarcomeres. The sarcomere is in charge of producing force.

Sarcomere is the basic unit which allows for skeletal muscle contraction and it is the region between two Z lines and from the Z line we have the actin thin filaments projecting towards the centre of the sarcomere and in the middle of the sarcomere we have the thick myosin filaments and this arrangement of the thick and thin filaments generates different zones of skeletal muscle

Question 12

Gross anatomy of skeletal muscle

Answer 12

Epimysium - Connective tissue sheathing the muscle
Endomysium - Protecting individual muscle fibers
Perimysium - Sheaths bundles of muscle fibers
Fascicles - Bundles of muscle fibers
Hundreds of myofibrils typically in one muscle fibre which contain contractile units known as myofilaments that are required for muscle contraction

5

Question 13

I Band

Answer 13

I band = only thin filaments,

I band region is the region between the myosin filaments so the I band only contains actin

Question 14

A Band

Answer 14

A band = stretches to either side of the M line, overlap of thick and thin filaments

In between the I band we have a region that contains both actin and myosin which s known as the A band. A band is defined by the length of the myosin and also contains some actin filaments.

Question 15

H zone

Answer 15

H-zone = only contains thick filament

only myosin thick filaments

It is important to note that when in the resting length the actin filaments do not protect all the way into the centre of the sarcomere and there is a little gap I there where there is just myosin and no acid and this space is the H zone

Question 16

Thick filament

Answer 16

Myosin

Question 17

Thin filament

Answer 17

Actin

Question 18

M line

Answer 18

M line is in the centre of the myosin and it contains proteins which basically organises and aligns the myosin which allows for its ordered arrangement

Question 19

Z line

Answer 19

Z line = mark the junction of actin filaments in adjacent sarcomeres

Question 20

Anatomy of a sarcomere

Answer 20

These different bands/zones change in length depending on the state of the muscle - it shortens when it contracts

When skeletal muscle contracts and shortens, the actin and myosin filaments slide over each other and it is the sliding of these filaments that creates the shortening

Question 21

Sarcomere in terms of a partially contracted muscle

Answer 21

Partially contracted muscle … As the muscle starts to contract, the Z discs come closer together and the myosin slides over the actin and some of these regions become smaller, specifically the H zone that just contains myosin and no actin because the actin filaments are slicing across each other and come closer together and the I band is also becoming smaller but the A band which is the area defined by the myosin stays the same

Question 22

Sarcomere in terms of a maximally contracted muscle

Answer 22

Maximally contracted muscle … can see it is maximally contracted because now the actin filaments have slid so far that they cannot go any further/pushed right up against the myosin - H zone is gone, I band is very tiny and the A band stays the same

Question 23

Muscles excitation problem

Answer 23

Skeletal muscles respond, they do not think therefore there is no intrinsic spontaneous activity (does not contract on its own)

Muscle fibers should contract near simultaneously along their entire length in order to create precise and controlled movements of our skeleton

Nervous system has developed a mechanism where we have neurons in the spinal cord and these motor neurons innervate skeletal muscle to generate the voluntary control but importantly for these large skeletal muscles we can have a single motor neuron that can innervate up to 1000 muscle fibres at once so you can imagine that you have multiple action potentials in one motor neuron and this single motor neuron can drive the coordinated and simultaneous contraction of skeletal muscle fibres and this way you have a very coordinated system

Question 24

NMJ also known as

Answer 24

motor endplate

Question 25

Neuromuscular junction

Answer 25

Neuromuscular junction - The myelinated axon of a motor neuron terminates at a single point on the muscle fibre. This specialised synapse is the NMJ. Also known as the motor endplate

Question 26

Structure of NMJ list

Answer 26

Axon 
Myelin 
Terminal
Schwann cell 
Active zone 
Vesicles (ACh) 
Sarcolemma 
Synaptic cleft 
Junctional folds (ACh esterase) 
ACh receptors 
Mitochondria

Question 27

Structure of NMJ - Myelin

Answer 27

Myelin - want high speed of action potential propagation in these icons so that as soo as we have an action potential in the spinal cord we can propagate it to the muscles extremely quickly

Question 28

Structure of NMJ - Terminal

Answer 28

Terminal - swelling enlargement of the icon close to the muscle fibre is known as the presynaptic nerve terminal

Question 29

Structure of NMJ - Schwann cell

Answer 29

Schwann cell - in the PNS, at the NMJ we have Schwann cells wrapping around synapses and help regulate synaptic transmission, these glial cells do not only give metabolic support, they can sense neurotransmitters in the synapse and they can also themselves release gliotransmitters to regulate the synapse

Question 30

Structure of NMJ - Active zone

Answer 30

Active zone - the release sites that have specialised proteins that bind to synaptic vesicles and allow for fusion

Question 31

Structure of NMJ - Vesicles (ACh)

Answer 31

Vesicles (ACh) - critical for neurotransmission and are packaged full of acetylcholine, present throughout the nerve terminal but the density of them is much higher close to the release sites (red on diagram) and some of them are even docked/tethered to the presynaptic membrane which means that when the action portential comes along and calcium comes into the nerve terminal there are these vesicles that are primed and ready to go which means that you can get a very fast and highly synchronised release of synaptic vesicles, the action potential does not directly drive secretion but it drives the opening of the voltage gated calcium channels and it is the calcium that drives exocytosis of these vesicles

Question 32

Structure of NMJ - synaptic cleft

Answer 32

Synaptic cleft - vesicles fuses with the membrane and releases its content into the extracellular space known as the synaptic cleft which is a very small space and the reason for it being so small is that it minimises the diffusion distance such that as you release the ACh it has a very tiny distance to diffuse to the other side therefore the speed of neurotransmission is fast

Question 33

Structure of NMJ - Sarcolemma

Answer 33

Sarcolemma - ACh is going to diffuse across the synaptic cleft and it is then going to bind to receptors on the postsynaptic membrane and in muscle this membrane has a specialised name called the sarcolemma

Question 34

Structure of NMJ - ACh receptors

Answer 34

ACh recceptors - the sarcolemma (plasma membrane of the muscle cell on the post synaptic side of the neuromuscular junction) has a very high density of these receptors

Question 35

Structure of NMJ - junctional folds (ACh esterase)

Answer 35

Junctional folds (ACh esterase) - infolds increase the surface area of the sarcolemma which means that you can have more receptors present and these also contain a very important regulating enzyme EACh esterase

Question 36

Structure of NMJ - Mitochondria

Answer 36

For energy

Question 37

Function of the NMJ

Answer 37

‘Synapse’ between motor neuron axon terminal and a muscle fibre

Action potentials in the motor neuron lead to depolarisation of muscle fibre via release of acetylcholine and it binding to the nicotinic receptors causes the depolarisation

Depolarisation of fibre triggers an action potential

1 action potential in terminal —> 1 action potential in muscle fibre unlike neurons
In NMJ, one action potential causes a significant depolarisation which is enough to cause an action potential in the muscle fibre
In the CNS, an action potential might cause slight depolarisation but not enough for it to reach threshold, in CNS you often need spatial or temporal summation in order to tiger an action potential as it has to reach threshold

Muscle fibre action potential trigger contraction (excitation-contraction coupling)

Question 38

Action potential in NMJ vs CNS

Answer 38

1 action potential in terminal —> 1 action potential in muscle fibre unlike neurons

In NMJ, one action potential causes a significant depolarisation which is enough to cause an action potential in the muscle fibre

In the CNS, an action potential might cause slight depolarisation but not enough for it to reach threshold, in CNS you often need spatial or temporal summation in order to tiger an action potential as it has to reach threshold

Question 39

Acetylcholine

Answer 39

Acetylcholine is a small molecule that acts as a chemical messenger to propagate nerve impulses across the neuromuscular junction between a nerve and a muscle.

Question 40

Synthesis and breakdown of acetylcholine

Answer 40

ChAT = choline acetyltransferase is the enzyme that synthesises ACh and CoA from acetyl CoA and choline
ACh esterase = acetylcholine esterase is in the junctional folds and it is important in the breakdown of ACh and once it is broken down it can no longer bind to the receptors which will terminate the process of polarisation, breaks ACh down into acetic acid and choline

Question 41

ChAT

Answer 41

ChAT = choline acetyltransferase is the enzyme that synthesises ACh and CoA from acetyl CoA and choline

Question 42

ACh esterase

Answer 42

ACh esterase = acetylcholine esterase is in the junctional folds and it is important in the breakdown of ACh and once it is broken down it can no longer bind to the receptors which will terminate the process of polarisation, breaks ACh down into acetic acid and choline

Question 43

Acetylcholine life cycle

Answer 43

Action potential triggers the release of EACh containing vesicle and have release of ACH into the synaptic cleft
It can bind to the post-synaptic receptors on the sarcolemma and these are nicotinic EACh receptors and this opens these receptors as an ion channel (they are ionotropic receptors) which causes the depolarisation of the post synaptic muscle cell

Extremely quickly the ACh is broken down by EACh esterase into acetic acid and choline and once broken down it cannot bind to any receptors anymore and therefore cannot cause a response it that cell anymore

It would not be very efficient if we had to synthesise new ACh all the time therefore there is a process where we can recycle the degradation products back into the nerve terminals so there are choline transporters that pump the choline back into the nerve terminal using gate help of the electrochemical gradient of the sodium influx and then ChAT takes choline plus acetyl CoA and makes ACH again and importantly the ACh produced then needs to be pumped into a very high concentration vesicle therefore need an active transporter put in to achieve the very high concentration of these vesicles

Question 44

What would happen if you inhibitied ACh esterase with drugs

Answer 44

If you inhibit AChesterase with drugs for example then you would cause ACh to stay in the synaptic cleft for much longer therefore would be binding to receptors for longer and causing depolarisation for longer and potentially more action potential in the skeletal muscle therefore this is one way that you can enhance skeletal muscle contraction