Physio (& pharma) of skeletal neuromuscular junction Flashcards
What is a motor unit?
The neurone and the number of fibres that it innervates are known as a motor unit
Describe he basic structure of the skeletal neuromuscular junction? Include it’s specialisations
Individual branches of the motor neurone axon further divide into multiple fine branches, each ending in a terminal bouton that forms a chemical synapse with the muscle membrane at the neuromuscular junction
What are the transmitters and receptors involved in the skeletal neuromuscular junction?
Action potentials arising in the cell body are conducted via the axon to the boutons causing the release of ACh.
The receptors are nicotinic ACh receptors
Outline the synthesis, storage and exocytotic release of acetylcholine (ACh)
Synthesis - ACh is synthesised in the cytosol from choline (transported in via choline transporter) and acetyl coenzyme A (acetyl CoA – supplied by mitochondria) by the enzyme choline acetyltransferase (ChAT, or CAT)
Storage - synaptic vesicles (containing and concentrating ACh) await release at active zones
Release - AP causes depolarization and the opening of voltage gated Ca channels - Ca causes “docked” vesicles to fuse with the presynaptic membrane and ACh diffuses into the synaptic cleft
Describe how activation of nicotinic ACh receptors causes the generation of the end plate potential (e.p.p.)
The nicotinic ACh rceptors havea central cation selective pore.
This pore opens when “ ACh bind to its exterior.
Na moves into the cell and K moves out. Movement of Na dominates.
Because the driving force for Na+ is greater than for K+ at resting membrane potential influx of Na+ is greater than efflux of K+: a depolarization known as the end plate potential (e.p.p.) is generated. Net influx of +ve charge
What does each unmyelinated branch of the motor neurone axon innervate?
an individual skeletal muscle cell (muscle fibre) within a muscle
What is the difference between an alpha motor neurone and a gamma motor neurone?
Alpha - bulk of muscle innervation for contractile force
Gamma - for muscle neurones for strength and length
What are the 4 key features of the skeletal neuromuscular junction?
- terminal bouton (and surrounding schwann cell)
- synaptic vesicles
- synaptic cleft
- end plate region of the muscle cell membrane (saarcolemma) thrown ino a series of junctional folds
What is the quantal nature of ACh release and how is this is formed from mepp?
How can mepp create epp and what does this initiate?
Each vesicle contains a “quantum” of neurotransmitter.
The electricall response to one quantu of transmitter is the miniature endplate potential (mepp).
Many m.e.p.ps summate to produce the end-plate potential (e.p.p) a graded (electronic) response
An e.p.p that exceeds threshold triggers an ‘all or none’ propagated action potential that give a “twitch” in the muscle.
Many epp creating APs required for muscle contraction.
What is the temporal relationship between the muscle AP and muscle contraction?
AP is musch briefer than each twitch it causes so AP gives little development of muscle tension.
Many APs give a tetanus response giving prolonged contraction.
How is neurmuscular transmission terminated by acetylcholinesterase (AChE)?
AChE (enzyme) hydrolyses ACh to choline and acetate,
choline is taken up by the choline transporter for re-synthesis of transmitter,
acetate diffuses from the synaptic cleft
What is neuromytonia? What is it’s AI origin? What drugs can be used to treat it?
- Multiple disorders of skeletal muscle function
- antibodies against voltage-activated K+ channels in the motor neurone disrupt function resulting in hyperexcitability (repetitive firing)
- Anti-convulsants - Carbamazepine, phenytoin
How does the AP spread from the NMJ?
With constant amplitude and velocity. It propagates over the surface membrane (sarcolemma) and then enters transverse (T) tubules. This triggers the release of Ca from the SR which in turn causes contraction by interacting with troponin associated with the myofibrils.
Where is AChE found?
Associated with the end plate membrane
What caracterises Lambert-Eaton Myasthenis Syndrome? What is it’s AI origin? What drugs can be used for treatment?
- muscle weakness in the limbs esp. proximal muscles
- antibodies against voltage-activated Ca2+ channels in the motor neurone terminal result in reduced Ca2+ entry in response to depolarization and hence reduced vesicular release of ACh
- anticholinesterases (pyridostigmine) and ptoassium channel blockers (3,4 diaminopyridine)
