Skeletal Muscle Flashcards
Briefly describe the anatomical composition and cellular features of skeletal muscle
Skeletal muscles are the muscle connected to bones and allow you to perform a wide range of movements and functions.
Individual muscle cells are called fibres. Skeletal muscles are composed of a highly ordered structure of long muscle fibers in one direction that allow for generating force via parallel contraction. Muscle fibres are rich in nerves, blood vessels and connective tissue.
Each muscle fibres is composed of a bundle of myofibril. Myofibers are comprised on repeating units called sarcomeres, which are the basic contractile units of a muscle. When a muscle contracts it is the Z-lines on either side of individual sarcomeres coming closer together.
Muscle contraction is primarily controlled by the interaction between two protein filaments within the sarcomere: actin and myosin. Actin filaments are thin and anchored to structures at the ends of the sarcomere called Z-lines, while myosin filaments are thicker and interdigitate with actin. Contraction occurs when myosin heads interact with actin, pulling the filaments closer together and shortening the sarcomere. This process is regulated by calcium ions released from the sarcoplasmic reticulum in response to nerve impulses.
Describe the structure of the neuromuscular junction
The neuromuscular junction (NMJ) is a synapse between a motor neuron axon terminal and a muscle fibre which allows for communication with a skeletal muscle fibre, allowing for voluntary muscle contraction. An AP moves down the myelin-coated axon and arrives at the pre-synaptic terminal. This triggers the movement of vesicles to the active zones, releasing acetylcholine (Ach). Ach moves into the synaptic cleft and down into the junctional folds. Ach then interacts with the receptors on the sarcolemma (cell membrane surrounding muscle fibre), depolarizing the fibre and propagating an AP. A muscle fibre AP triggers contraction via process known as excitation-contraction coupling. One AP in terminal leads to one AP in the muscle fibre – this is different to neurons in the CNS which usually get multiple AP from the same input.
State the function of acetylcholine at the neuromuscular junction and describe its “life cycle”
Ach is a neurotransmitter that plays a role in involuntary muscle movement. When an AP reaches the pre-synaptic terminal of a skeletal muscle it triggers the release of Ach into synaptic cleft and into junctional folds. Ach the interacts with the receptors on the sarcolemma which is the cell membrane of the muscle fibre. Ach depolarizes the fibre trigger contraction.
Ach life cycle refers to the synthesis and breakdown of the neurotransmitter. Once Ach is released into the synaptic cleft and activated Ach receptors on the sarcolemma, the signal is terminated by using AchE which breaks the Ach down into acetic acid and choline. The choline from breakdown is then transported by choline transported back into the pre-synaptic (coupled with sodium). Once the choline is inside the cell we use ChAT to generate more Ach which is put into vesicles.
The Ach can be generated completely inside the cell but this lifecycle of synthesis and breakdown is more efficient in time and energy.
What is a muscle cell called?
Fibre
Fibres are structured in one direction - what type of contraction does this result in?
Parallel contraction
What is skeletal muscle rich in?
nerves
blood vessels
connective tissue
What is a sarcomere?
An individual contractile units of skeletal muscle.
What is a myofibril made up of?
Repeating units of sarcomeres.
What is the cell membrane of a muscle fibre called?
Sarcomella
Between filaments of myosin and actin what one is thick and what one is thin?
Myosin is the thick filament. Actin is the thin filament.
Is there intrinsic spontaneous activity in muscles?
No - they require being told / stimulus.
Whats the junction between motor neuron axon and muscle fibre called?
Neuromuscular Junction (NMJ)
What is the benefit of junctional folds on the muscle fibres?
Increases surface areas for more acetylcholine receptors (to be stimulated by Ach released from pre synaptic motor neuron) which initiates contraction.
What is the active zone?
Where the Ach interacts.
How many AP do you need to generate an AP in muscle fibre?
1
What is the chemical synthesis of ACh?
Acetyle CoA + Choline (using ChAT) = ACh + CoA
What is the chemical breakdown of ACh?
ACh is broken down using AchE = Acetic acid + Choline
What is coupled to choline transporter when moving choline back into cell?
Sodium
Is ChAT or AchE inside the cell?
ChAT
Describe the sequence of events in the pre synaptic motor neuron that initiate skeletal muscle contraction (9 steps)
(1) AP in axon, (2) Opens voltage gated calcium channels and calcium enters, (3) Calcium triggers vesicle fusion e.g., exocytosis, and the release of Ach, (4) Ach binds to nAchR on the muscle fiber, (5) nAchR channels open and sodium enters, (6) local depolarization spreads to extra junctional membrane, (7) depolarization opens the voltage gated sodium channels and AP triggered, (8) AP propagates down the muscle fiber, (9) Ach degraded by AchE.
Describe the structure and function of acetylcholine receptors
The acetylcholine receptor specific to the neuromuscular junction is nicotinic acetylcholine receptors. Nicotinic Ach receptors have five subunits each with four transmembrane domains. The bundle of the subunits create the pore in the membrane. The pore is chemically gated. It is normally closed to prevent any unwanted depolarization that has not been signaled for. It opens when two Ach neurotransmitters bind to it. The channel is non-selective to cations meaning that both Na+ and K+ pass through it when opened (a lot more Na+ than K+ due to electrochemical gradients). The large gradient for sodium is what caused depolarization when the channels are opened.
Understand the role of the neuromuscular junction in Myasthenia gravis
Myasthenia gravis (MG), also known as graves’ muscle disease, is an autoimmune disease of the neuromuscular junction which ultimately causes weakness to skeletal muscles that are under voluntary control. An autoimmune disease is where your own body mistakes something that is meant to be functioning in the body as foreign and attacks it by breaking down the receptors.
The antibodies reduce the number, block, and cause inflammation to the nAchR. This results in reduced NMJ function and therefore weakness to muscles and in particular those frequently used such as the face muscles. This is because less nAchR receptors means that it is harder for signal from a nerve to reach and activate the muscle fibre.
It affects more frequently used muscles more because as more signals are sent to the nerve terminal resulting in the release of Ach (but then the Ach not activating anything as receptors are not functioning) over time it results in a depletion of Ach in vesicles. When less Ach is released, the receptors being activated is even less likely as it is a numbers game.
One way that MG can be treated is by delaying the breakdown of Ach, so that Ach levels can build up. This works by letting Ach hang around in the synaptic cleft for longer before it is broken down. This allows for a greater quantity to build up and be put back in the vesicles before being released again. Then there re is more likelihood that a muscle fiber will be activated with each depolarization.
What receptor is involved in the neuromuscular junction?
Nicotinic acetylcholine receptor (nAchR).
How many subunits does the nAchR have?
5, with 4 transmembrane domains (meaning it spans across the membrane)
When does the nAchR open?
When two Ach bind
What else is the nArchR permeable to?
Na+ and K+ (the large gradient for Na+ drives depolarisation)
What is the agonist to the nArchR?
Nicotine
What is the antagonist to the nAchR?
a-tubocurarine (plant)
Alpha-neurotoxins (poison found in snakes)
What is an autoimmune disease?
An autoimmune disease is where your own body mistakes something that is meant to be functioning in the body as foreign and attacks it by breaking down the receptors.
What is the byproduct of activating the immune system?
Inflammation
What does ‘safety factor’ of Myasthenia Gravis refer to?
Safety factor is the high stores of Ach and Ach receptors which means that it is very unlikely for Ach stores to be depleted even when we contract the same muscles over and over again.
What do we inhibit to prolong the breakdown of Ach in synaptic cleft?
We inhibit the AchE (esterase) enzyme.
