Physiology of Skeletal Neuromuscular Junctions 03/10/18 Flashcards
What is the only voluntary muscle?
Skeletal
What innervates the skeletal muscle?
Motor neurones with myelinated axons and cell bodies in the spinal cord
What does the motor neurone axon branch into near the muscle?
Unmyelinated branches
What does each unmyelinated branch innervate?
A single skeletal muscle fibre
What does each motor neurone branch end in?
Terminal bouton that forms a chemical synapse with the NMJ
What is the path of an action potential in a skeletal muscle fibre?
Arise in the cell body
Conducted via the axon
Causes release of ACh
What is the neurotranmitter for all skeletal muscle fibres and what receptor does it act of?
Acetylcholine
On Nicotinic receptors
What are the key features of a NMJ?
Terminal bouton (and surrounding schwann cell)
Synaptic vesicles
Synaptic cleft
End plate region of the muscle cell membrane
Where are synaptic vesicles and what do they contain?
Active ones
ACh
Where are nicotinic receptors present?
End plate region
Give and overview of synaptic transmission at the NMJ
Ach is stored in active vesicles, these build up
calcium causes this to be released
Activating the nicotinic receptor
The transmitter in inactivated
How is choline transported into the terminal?
Choline transport symport with Na+
What synthesises ACh and where does it occur?
Choline and acetyl coenzyme A
In the cytosol
By choline acetyltransferase
How is ACh concentrated into vesicles?
Vesicular ACh transporter
What does arrival of the action potiential at the terminal cause?
Depolariation and opening of voltage-activated Ca2+ channel allowing Ca entry to the terminal
What does calcium do to the vesicles?
They fuse with the presynaptic membrane (exocytosis) - Ach diffuses into the synaptic clept to activate post-synaptic nicotinic Ach receptors
What is the arrangement of nicotinic Ach receptors?
Pentamer of glycoprotien subunits that surround a centeral cation
What is contained in the centeral cation pore?
A gate that is closed in the absence of ACh
Where does ACh bind?
Interphase between subunits (alpha gamma and alpha 8?)
What efflux/influx occurs when the gate is open/
Na+ influx
K+ Efflux
This causes the intercellular region to become less negative - end plate potential
What makes the end plate potential?
ACh binding to nicotinic receptors
Does each vesicle have the same amount of ACh molecules in it and what is it called?
yes this is known as the quantum
What happens when multiple vesicles release their quantum?
It has a combined affect on the voltage, causing a large depolarization building up - known as the end plate potential
How does the end plate potential produce contraction?
The end plate potential reaches a threshold potential, leading to the opening of voltage activated sodium channels, which triggers a muscle action potenitial
Which is graded, end plate potential or action potential?
End plate potential
What can reduce the amplitude of the EPP?
Drugs
Toxins
What happens when an end plate potential doesn’t reach the threshold?
No contraction occurs
Fibre spreads out
Loses size
Fades away to nothing
What are the symptoms of neuromyotonia?
Multiple disorders of skeletal muscle function including cramps, stiffness, slow relaxation (myotonia) and muscle twitches
What is the cause of neuromyotonia?
Mostly autoimmune - antibodies against voltage-activated K+ channels in the motor neurone resulting in hyperexcitability (repeated fitting)
What are the drug treatments for neuromyotonia?
Anti-convulsants
carbamazepine
Phenytoin
What are the characteristics of Lamber eaton myasthenic syndrome?
Muscle weakness in the limbs
?Small cell carcinoma of the lung
What is the cause of LEMS?
Autoimmune - antibodies against voltage activated Calcium channels in the motor neurone terminal result in reduced cancium centry
What is the drug treatment for LEMS?
Antcholinesterases and potassium channel blockers
What are the characteristics of Myasthenia gravis?
Progressivley increasing muscle weakness during periods of activity
Presents with weakness of the eye and eyelid
What is the cause of Myaesthenia gravis?
Autoimmune - antibodies against nicotinic ACh receptors in the endplate result in reduction in the number of functional channels and hence the amplitude of the end plate potential
