Lecture 9 - Skeletal muscle neurophysiology I Flashcards
Control of skeletal muscle
voluntary
what does skeletal muscle act on
acts on the skeleton and the body has this muscle so that it can move and interact with the environment
thin and thick filaments of skeletal muscle cause a what
a striation pattern
Movements of skeletal muscle
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
Flexion
Flexion = reducing the angle between two bonds, involves activation of flexor muscles and relaxation of extensor muscles
Extension
Extension = making the angle larger between two bones, going further apart, involves the activation/contraction of extensor muscle and the relaxation of flexor muscles
Origin and insertion
Proximal insertion that attached to the bone is called the origin and the distal end that attaches to bone is called the insertion
tendons
Tendons connect you skeletal muscle to you skeleton and the tendons allow for muscles to exert force on the skeleton
Skeletal muscle fibre anatomy
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
Myofibrils are made up of
repeating subunits called sarcomeres
Sarcomere is an
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
Gross anatomy of skeletal muscle
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
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I Band
I band = only thin filaments,
I band region is the region between the myosin filaments so the I band only contains actin
A Band
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.
H zone
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
Thick filament
Myosin
Thin filament
Actin
M line
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
Z line
Z line = mark the junction of actin filaments in adjacent sarcomeres
Anatomy of a sarcomere
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
Sarcomere in terms of a partially contracted muscle
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
Sarcomere in terms of a maximally contracted muscle
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
Muscles excitation problem
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
NMJ also known as
motor endplate
Neuromuscular junction
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
Structure of NMJ list
Axon Myelin Terminal Schwann cell Active zone Vesicles (ACh) Sarcolemma Synaptic cleft Junctional folds (ACh esterase) ACh receptors Mitochondria
Structure of NMJ - Myelin
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
Structure of NMJ - Terminal
Terminal - swelling enlargement of the icon close to the muscle fibre is known as the presynaptic nerve terminal
Structure of NMJ - Schwann cell
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
Structure of NMJ - Active zone
Active zone - the release sites that have specialised proteins that bind to synaptic vesicles and allow for fusion
Structure of NMJ - Vesicles (ACh)
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
Structure of NMJ - synaptic cleft
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
Structure of NMJ - Sarcolemma
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
Structure of NMJ - ACh receptors
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
Structure of NMJ - junctional folds (ACh esterase)
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
Structure of NMJ - Mitochondria
For energy
Function of the NMJ
‘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)
Action potential in NMJ vs CNS
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
Acetylcholine
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.
Synthesis and breakdown of acetylcholine
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
ChAT
ChAT = choline acetyltransferase is the enzyme that synthesises ACh and CoA from acetyl CoA and choline
ACh esterase
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
Acetylcholine life cycle
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
What would happen if you inhibitied ACh esterase with drugs
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
