What two receptor types are found in abundance on the post synaptic membrane found at the NMJ?
Voltage gated sodium
nAchR
Voltage gated calcium
NMDA
What is the correct process of synaptic transmission?
Action potential received at pre-synaptic terminal -> Ca2+ entry due to VG Ca2+ open -> binds to synaptotagmin -> conformational change -> Ach vesicles fuse with pre-synaptic membrane.
Ca2+ entry -> Action potential produced -> Ach vesicles fuse with the pre-synaptic membrane.
When Ach binds to the post-synaptic membrane, the resting membrane potential of the muscle cell goes from -90mV to...
-20mV
+10mV
0mV
-55mV
Binding of Ach causes production of an end plate potential. How does this end plate potential permit the subsequent initiation of an action potential?
The EPP causes voltage gated sodium channels to open which leads to an action potential being produced in the muscle cell.
The EPP causes voltage gated chloride channels to close which leads to an action potential being produced in the muscle cell.
Acetylcholine is recycled from the synaptic cleft as what two components?
Acetate
Choline
Chlorine
Acetyl
What enzyme reincorporates the two components of Ach back into Ach?
Cholineacetyltransferase
Acetylcholinetransferase
Acetylcholinesterase
After the initiation of an end plate potential and subsequent action potential, how does this action potential resulting in calcium efflux from the sarcoplasmic reticulum?
The action potential travels down T-tubules. A receptor called the DHP receptor (a voltage sensor) detects this voltage change and undergoes a conformational shape change. This conformational change leads to unplugging of ryanodine from the sarcoplasmic reticulum which allows mass efflux of calcium from the sarcoplasmic reticulum.
The action potential travels down T-tubules. A receptor called the DNP receptor (a voltage sensor) detects this voltage change and undergoes a conformational shape change. This conformational change leads to unplugging of ryanodine from the sarcoplasmic reticulum which allows mass efflux of calcium from the sarcoplasmic reticulum.
What is the function of the light chain of botulinum toxin?
The light chain binds to the pre-synaptic membrane at the point where neurotransmission is occuring. This causes the botulinum toxin to be up-taken into the pre-synaptic terminal.
The light chain is a protease which cleaves proteins that are fundamental for exocytosis of neurotransmitter to occur. This therefore means that exocytosis of neurotransmitter does not occur and the muscle remains paralysed.
What is the function of the heavy chain of botulinum toxin?
The heavy chain binds to the pre-synaptic membrane at the point where neurotransmission is occuring. This causes the botulinum toxin to be up-taken into the pre-synaptic terminal.
The heavy chain is a protease which cleaves proteins that are fundamental for exocytosis of neurotransmitter to occur. This therefore means that exocytosis of neurotransmitter does not occur and the muscle remains paralysed.
Very active muscle fibres are amongst the first to be affected by botulinum toxin.
Name a depolarising blocker of the NMJ
Tubocurarine
Pancuronium
Suxamethonium
Hexamethonium
Give two examples of non-depolarising neuromuscular junction blockers
Anti-cholinesterases can cause suxamethonium-like properties in the synaptic cleft.
What are anti-cholinesterases used for treatment of myasthenia gravis?
Auto-antibodies that bind to nAchR's at NMJ's which are indicated in Myasthenia Gravis compete for the agonist binding site (Ach being the agonist). By using an anti-cholinesterase, you increase the amount of Ach present in the synaptic cleft which can out-compete the auto-antibodies for the nAchR binding site and thus reverse the inhibitory effects.
Auto-antibodies that bind to nAchR's at NMJ's which are indicated in Myasthenia Gravis compete for the agonist binding site (Ach being the agonist). By using an anti-cholinesterase, you increase the amount of Ach present in the synaptic cleft which can out-compete the auto-antibodies for the nAchR binding site and thus reverse the excitatory effects.
Although suxamethonium is a depolarising NMJ blocker, it is broken down more slower than Ach and therefore sustains depolarisation of the muscle cells, leading to fasciculations.
Suxamethonium leads to paralysis because the sustained depolarisation that it causes eventually leads to inactivation of VG Na+ channels.
Myosin heads have GTPase activity that can hydrolyse GTP to recock the myosin head.
What are the three main energy systems of muscle contraction?
Phosphocreatine
Lactic acid
Oxidative phosphorylation
Substrate level phosphorylation
Glycogenolysis
Slow twitch fibres mostly take part in anaerobic respiration.
Phosphocreatine is broken down to get inorganic phosphate that can be used in ATP that partakes in muscle contraction.
Pumping of Ca2+back into the sarcoplasmic reticulum to aid in relaxation of the muscle fibre requires ATP.
A motor unit is...
A motor neurone that innervates severe muscle cell sarcomeres to produce co-ordinated responses
A group of motor neurones that innervate a single muscle cell each to produce co-ordinated responses
If there is a large force required for a muscle to carry out a task, would slow twitch or fast twitch fibres be used?
Fast twitch
Slow twitch
Recruitment of motor units describes what?
Increasing the number of motor units firing
Increase the frequency of motor units firing
Rate coding of motor units describes what?
Increasing the frequency of motor units firing
Name some examples of neurogenic motor unit disease
Guillain-Barre syndrome
ALS
Duchenne muscular dystrophy
Dermatomyositis
Name some examples of myopathic motor unit diseases
Most treatment for ALS (motor neurone disease) is symptomatic.
ALS affects what part of the motor system?
Upper motor neurones
Lower motor neurones
Sensory neurones
What symptoms can ALS present?
Weakness
Wasting
Fasciculation
Cognitive decline
Guillain-Barre syndrome affects what aspects of the motor system?
Peripheral motor neurones
Guillain-Barre is due to cross-reacting antibodies that attack peripheral nerves.
How could you treat Guillain-Barre?
Plasma exchange to get rid of cross-reacting antibodies
Intravenous immunoglobulin to try to get rid of cross-reacting antibodies
Intraneurone injection to stimulate nerve regrowth
What is responsible for DMD?
The dystrophin protein which anchors intracellular actin to the muscle membrane.
A mutation in the dystrophin protein which leads to failed anchorage of intracellular actin to the muscle membrane.
DMD leads to muscle wasting and weakness.
Serum creatine kinase levels are an indicator of muscle damage in DMD.
