Physiology of the skeletal neuromuscular junction Flashcards
What type of motor neurones innervate skeletal muscle?
Myelinated axons with cell bodies in the spinal cord or brain stem
When will the myelinated axons become unmyelinated?
When they are close to the muscle
What is the neurotransmitter at neuromuscular junctions?
ACh
What type of cell surrounds every terminal bouton?
Shwann cels
What type of receptor is present at the post-synpatic membrane?
Nicotinic receptors
Where can vesicles of ACh be found in the pre-synaptic terminal?
In the active zone
What is the process in a neuromuscular synapse?
Synthesis of ACh
Process of ACh into vesicles
Movement of vesicles to active zone
Release of ACh when an action potential travels through the membrane causing the opening of Ca2+ channels, this causes the release of ACh from the vesicels into the synaptic cleft
ACh acts on nicotinic receptors and then is subsequently broken down
How is choline transported into the pre-synaptic terminal?
By a choline transporter that also transports Na+
How is ACh synthesised?
From choline and acetly CoA by ChAT
Where is acetly CoA derived from?
Mitochondria
What is the action of calcium in the pre-synaptic terminal?
Causes vesicles docked at the active zone to fuse with the presynaptic membrane to allow ACh to dissue into the synaptic cleft
This allows ACh to activate post-synaptic nicotinic receptors in the endplate region
What is the structure of nicotinic receptors?
5 subunits of glycoproteins (2x alpha, beta, gamma and delta)
What occurs when the nicotinic gate opens?
Na+ enters the muscle cell and K+ leaves
When will nicotinic receptors open?
When 2 molecules of ACh bind to it
How is the end plate potential generated?
The driving force for sodium is greater than that for potassium and therefore the membrane will be depolarised (voltage gets more positive)
If this is large enough, this will trigger the opening of Na+ channels around the end plate causing an all or nothing action potential
What will one action potential in the motor nerve trigger?
One action potential and a subsequent twitch
What effect will the action potential have on the muscle cell?
Will enter T tubules and cause release of calcium from the lateral sacs of the SR
Calcium will bind to troponin-tropomyosin complex allowing for the power stroke
How is the action of ACh terminated?
Via AChE enzyme present at the end plate membrane that will break down ACh to choline and acetate
What are the symptoms of neuromyotonia?
Cramps
Stiffness
Myotonia
Muscle twitches
What is the effect does neuromyotonia have on the neuromuscular junction?
Autoantibodies against voltage-activated K+ channels in the motor neurone disrupting function causing repetitive firing
How is neuromyotonia treated?
Anti-convulsants - carbamazepine and phenytoin which block Na+ channels
What are the symptoms of lambert-eason myasthenic synrome?
Muscle weakness in limbs
Associated with small cell carcinoma of the lung
What is the effect does LEMS have on the neuromuscular junction?
Autoantibodies against Ca2+ channels in the motor neurone terminal resultin gin reduced calcium entry in response to depolarization and hence reduced ACh release
How is LEMS treated?
Anticholinesterases and potassium channel blockers
Increase conc of ACh within the synaptic cleft
What are the symptoms of myasthenia gravis?
Increasing muscle weakness during periods of activity
Often weakness of eye and eyelid
What is the effect does myasthenia gravis have on the neuromuscular junction?
Autoantibodies against nicotinic ACh receptors in endplate resulting in reduced number of functional channels and hence amplitude of e.p.p.
How is myasthenia gravis treated?
Anticholinesterases and immunosuppressant agents (azathioprine)
What is the effect does botulinum toxin have on the neuromuscular junction?
Exotoxin toxin that acts at motor neurone termins to irreversibly inhibit ACh release
Enzymatically modifies proteints on docking vesicles in active zone
