Behavior of Skeletal muscle fibers

Role of ACh

A neurotransmitter that plays a key role in triggering muscle contraction at the NMJ.

• Binding

  ACh binds to a receptor molecule in the muscle fiber's postsynaptic membrane.

• Channel opening

  This binding changes the membrane's permeability, causing channels to open that allow sodium ions to flow into the muscle cell.

• Muscle contraction

  If enough nerve impulses accumulate, the sodium channels become fully activated, causing the muscle cell to contract. 

Role of synaptic vesicles

Play a key role in the NMJ by storing and releasing neurotransmitters that transmit nerve impulses between neurons and muscles.

• Storage: SVs store neurotransmitters in the presynaptic terminal's reserve pool. 

• Release: SVs are released in response to increased intracellular calcium concentration. This process involves docking, priming, and fusing with the presynaptic membrane.

Role of ACh receptors

Translates electrical signals from motor neurons into muscle contractions.

• Location

  ACh receptors are located at the top of the junctional folds in the postsynaptic membrane of the muscle fiber. 

• Function

  When ACh binds to the receptors, it opens sodium channels that allow sodium ions to flow into the muscle membrane. This creates an endplate potential that triggers a muscle action potential. 
  

Role of acetylcholinesterase (ACHe)

To rapidly breakdown ACh, the neurotransmitter responsible for muscle contraction, effectively terminating the signal and allowing the muscle to relax after contraction by quickly removing ACh from the synaptic cleft; essentially, it acts as a "cleanup" enzyme to ensure a precise and brief muscle response.

Flaccid paralysis vs Spastic paralysis

Flaccid paralysis: Muscles that prevent from contracting ex: curare (plant poison), Botox (paralyzes muscle)

Spastic paralysis: Muscles activated but no conscious control ex: tetanus (bacteria), black widow spider venom, cholinesterase inhibitors

Action potential

An action potential in a muscle is a rapid electrical signal that travels across the muscle cell membrane, causing a change in voltage which ultimately triggers the muscle to contract, essentially, it's the electrical impulse that initiates muscle movement.

Finishing opening all channels in excitation.

Neuromuscular junction:

In most cases, an action potential in a muscle is triggered by a signal from a motor neuron at the neuromuscular junction, where neurotransmitters like acetylcholine are released.

Muscle excitation steps

1. Arrival of nerve signal (nerve signal arrives + Ca enters)

2. AcH release

3. Binding of ACh to receptor

4. Opening of ligand-regulated ion gate, creation of end plate potential (EPP) - more sodium goes in which changes membrane potential - becoming less negative

5. Opening of voltage-regulated ion gates; creation of action potentials - sodium comes in and allows more channels to come in - Depolarization

Ligand

Chemical that binds to receptor

Depolarization

Membrane becomes less negative due to sodium influx

Ex: Sodium

Repolarization

Membrane becomes more negative due to potassium influx

Ex: Potassium

Excitation-contraction coupling

6. Action potentials propagated down T tubules

7. Calcium released from terminal cisternae

8. Binding of calcium to troponin

9. Shifting of tropomyosin, exposure of active sites (sites on actin) on actin

Contraction

10. Hydrolysis of ATP to ADP + Pi; activation and cocking of myosin head -—> extends head

11. Formation of myosin-actin cross bridge -—> binds to nearest site of actin

12. Power stroke; sliding of thin filament over thick filament —> release of ADP + Pi

13. Binding of new ATP, breaking of cross bridge

A cycle!!

Muscle relaxation

14. Cessation of nervous stimulation and ACh release

15. ACh breakdown of AChE —> in synaptic cleft

16. Reabsorption of calcium ions by sarcoplasmic reticulum —> calcium pumps

17. Loss of calcium ions from troponin

18. Return of tropomyosin to position blocking active sites of actin

When sarcomere shorten…

1. Normal sacromere

2. H band and I band width decreased

3. No more H band, I band shortened

A band—> does not change

H & I band—> do change