NMJ- lecture 15

NMJ structure

• presynaptic terminal (motor neuron axon)

• synaptic cleft (space between the two)

• postsynaptic membrane (muscle fibers motor end plate)

presynaptic terminal

contains vesicles of acetylcholine and transmits signals to another neuron or target cell

synaptic cleft

gap between two neurons allowing communication

b

b

What are the three main structural parts of the neuromuscular junction (NMJ)?

Presynaptic motor neuron terminal, synaptic cleft, postsynaptic motor end plate.

What neurotransmitter is released at the NMJ?

Acetylcholine (ACh).

What enzyme breaks down acetylcholine in the synaptic cleft?

Acetylcholinesterase (AChE).

What type of receptor is located on the motor end plate?

Nicotinic acetylcholine receptor (ligand-gated ion channel).

Which ion enters the presynaptic terminal to trigger ACh release?

Calcium (Ca²⁺).

What happens when ACh binds to nicotinic receptors?

Sodium enters, potassium exits, causing an end-plate potential (EPP).

How does the end-plate potential lead to muscle contraction?

EPP triggers voltage-gated Na⁺ channels → AP spreads → T-tubules → Ca²⁺ release from SR → contraction.

What is the role of T-tubules in neuromuscular transmission?

Conduct action potentials deep into the muscle fiber to trigger Ca²⁺ release.

Step 1 of neuromuscular transmission

Action potential arrives at presynaptic motor neuron terminal.

Step 2 of neuromuscular transmission

Depolarization opens voltage-gated Ca²⁺ channels in presynaptic terminal.

Step 3 of neuromuscular transmission

Calcium ions enter the presynaptic terminal.

Step 4 of neuromuscular transmission

Synaptic vesicles fuse with presynaptic membrane via SNARE proteins.

Step 5 of neuromuscular transmission

Acetylcholine (ACh) is released into synaptic cleft by exocytosis.

Step 6 of neuromuscular transmission

ACh diffuses across the cleft.

Step 7 of neuromuscular transmission

ACh binds to nicotinic ACh receptors on the motor end plate.

Step 8 of neuromuscular transmission

Ligand-gated Na⁺/K⁺ channels open → end-plate potential (EPP) generated.

Step 9 of neuromuscular transmission

End-plate potential reaches threshold → voltage-gated Na⁺ channels open → AP in muscle fiber.

Step 10 of neuromuscular transmission

Action potential propagates along sarcolemma and down T-tubules.

Step 11 of neuromuscular transmission

DHP receptors activate ryanodine receptors on sarcoplasmic reticulum.

Step 12 of neuromuscular transmission

Calcium released into sarcoplasm from SR.

Step 13 of neuromuscular transmission

Calcium binds troponin → tropomyosin shifts → cross-bridge cycling begins (contraction).

Step 14 of neuromuscular transmission

Acetylcholine is broken down by acetylcholinesterase, ending stimulation.

Step 15 of neuromuscular transmission

Calcium is pumped back into the SR, leading to muscle relaxation.

How does botulinum toxin affect NMJ transmission?

Blocks ACh release, causing flaccid paralysis.

How does curare affect NMJ transmission?

Blocks nicotinic ACh receptors, preventing depolarization and causing paralysis.

How does succinylcholine work at the NMJ?

Causes prolonged depolarization (depolarizing block) → fasciculations → flaccid paralysis.

What is the mechanism of neostigmine at the NMJ?

Inhibits acetylcholinesterase, prolonging ACh action and improving transmission, increases ACh in nmj.

Which drug blocks choline uptake into the presynaptic terminal?

Hemicholinium.

What is the physiological consequence of AChE inhibition?

Increased ACh in cleft, prolonged stimulation of receptors, stronger or prolonged muscle contraction.