NMJ & Excitation

What is A

Neuromuscular junction

How many motor neurons does a muscle fibre receive input from

1

Where do muscle fibres receive input from motor neurons

At a single synapse (neuromuscular junction)

Near the centre of the muscle fibre, roughly equidistant from the two tendons

*Excitation Contraction Coupling*

Represents physiologic mechanism whereby an electrical discharge at muscle initiates chemical events at cell surface to release intracellular Ca2+ and produce muscle action

(Associated with myosin actin interaction)

What is released from the somatic motor neuron

ACh

Role of ACh in excitation contraction coupling

Open ligand (chemical) gated channels

What runs through the ligand gated channels

Na+ diffuses in, producing depolarising stimulus (action potential produced)

Where are a high density of receptors found

In folds of sarcolemma

Neuromuscular junction

site where a motor neuron stimulates a muscle fibre

Motor end plate

area of the muscle fibre sarcolemma where a motor neuron stimulates it

What happens at the neuromuscular junction

How do vesicles bind with the presynaptic membrane

They are both lipid based

Role of Acetylcholinesterase

Acetylcholinesterase is responsible for breaking down acetylcholine in the receptors and the cleft. It breaks down acetylcholine into acetate and choline.

Label

1. Schwann cell

2. Synaptic vesicles

3. Axon terminal

4. Synaptic cleft

5. Schwann cell process

6. Muscle cell

7. Acetylcholine molecule

8. Postjunctional fold

9. Nicotinic acetylcholine receptors in postjunctional membrane

ESPS

Excitatory Postsynaptic Potential

(What is the electrical activity at the neuromuscular junction when there is a change in motor axon action potential) Picture

Any substance that affects Acetycholine transmission will affect __________

Muscle contraction

How does botulism toxin (BOTOX) work and what is it used for

Inhibits acetylcholine release from nerve terminal

Used for:

• Focal Dystonias,

• Spasticity in cerebal palsy

• Cosmetic surgery

How does curare work and what is it used for

Blocks AChR receptor

Used on poison arrows in South America

Acetycholinesterase inhibitors (e.g. neostigmine) are used to treat myasthenia gravis which is …..

Grave muscle weakness

What else treats myasthenia gravis other than Acetycholinesterase inhibitors (e.g. neostigmine)

Plasmapheresis (plasma exchange

Cause of myasthenia gravis

Autoimmune disease - Immune system does not recognise the ACh Receptors as self and so attacks and diminishes the density of these receptors at the NMJ.

Symptoms of myasthenia gravis

Patients have flaccid & loose muscles - find it difficult to find muscle fibres to contract

Prevalence of myasthenia gravis

1:5000

Botox capital of the world

Westport (in bacteria)

Result of inhibition of Acetycholinesterase in the synaptic cleft

Inhibition of Acetycholinesterase -> less degradation of ACh.
ACh increases in the synaptic cleft and compensates for the low numbers of Ach Receptors

Process of excitation contraction coupling

1. Sarcolemma

2. Terminal cisternae

3. Transverse tubule

4. Sarcoplasmic reticulum

5. Mitochondria

6. Myofibrils

7. A band

8. I band

9. Z line

10. Nucleus

Transverse Tubules

Narrow membranous tunnels formed from the sarcolemma

Transverse Tubules role

Open to the extracellular environment
Able to conduct action potentials

Sarcoplasmic Reticulum (SR) vs Endoplasmic reticulum

SR is modified endoplasmic reticulum that stores Ca2+ when muscle is at rest

How does Ca2+ diffuse out of the SR when a muscle fibre is stimulated

via calcium release channels
(Ryanodine receptor; RyR)

How does the Ca2+ supply in the SR get replenished

At the end of a contraction, Ca2+ is actively pumped back into the SR by the Ca2+- ATPase pump.

1. Myofibril

2. Sarcoplasmic reticulum

When is the Ca-ATPase pup active

Constantly - tightly regulates calcium levels

What percentage of ATP is used by the Ca-ATPase pump and the Cross bridges

30% Ca-ATPase pump

70% cross bridges

Process of Stimulating a Muscle Contraction

-Acetylcholine is released from the motor neuron.
• End plate potentials are produced.
• Action potentials are generated.
• Voltage-gated calcium channels (DHPR) in transverse tubules change shape and cause calcium channels in SR to open.
• Calcium is released and can bind to troponin C
• Cross-bridges bind, rotate and generate force (70% ATP)

Process of Muscle Relaxation

-Action potentials cease.
• Ca2+-ATPase pumps Ca2+ back into SR (30% ATP).
• No more Ca2+ is available to bind to troponin C, so no more cross bridges are formed.

Temporal sequence of events in excitation-contraction coupling

1. Action Potential

2. Intracellular (Ca²⁺)

3. Tension

(An Action Potential precedes the rise in Ca2+, which precedes cross-bridge cycling resulting in
force development)