NMJ Flashcards
What is the Neuromuscular Junction (NMJ) anatomy?
- Presynaptic terminal
- Synaptic vesicles with ACh in the presynaptic terminal
- calcium channels on the presynaptic membrane
- synaptic cleft
- Postsynaptic membrane (skeletal muscle cell)
- receptors on postsynaptic membrane for ACh
What kind of Ca2+ channels are on the presynaptic membrane?
P/Q type Ca channels
What is the name of the receptors on the postsynaptic membrane?
nmAChR- nicotinic cholinergic receptor
What is the postsynaptic membrane cell?
Skeletal muscle cell
How many ACh does the nmAChR require to activate?
2 ACh
What kind of cation channel is nmAChR?
Non-specific mixed cation channel (Na+ and K+)
What is the flow of Na+ and K+?
Na+ flows inside the cell
K+ flows outside the cell
What are the sizes of the force of Na+ and K+? What does it trigger?
Fk= very small
Fna= very large
–> nmAChR activation, Na+ influx–> depolarization
What is the function of NMJ?
Nerve AP–> muscle AP (MAP)
What does EPP is “graded” mean?
Not “all or nothing” event
What increases the size of EPP?
more ACh-> higher EPP
By triggering EPP, what is the result?
Muscle AP (MAP)
What are the 3 steps of Termination of an EPP?
- Stop exocytosis of ACh
- ACh dissociates from nmAChR
- ACh removed
How is exocytosis of ACh stopped?
Ca2+ diffuses away from vesicles:
[Ca2+]inside - ATPase pumps–> [Ca2+] outside
What happens when ACh dissociates from nmAChR?
nmAChR deactivates -> EPP dissipates
How is ACh removed?
- diffuses away
- enzymatic breakdown in cleft by AChE
What is AChE?
Acetylcholineesterase- breaks down ACh to choline and acetate
What are the 2 steps of Recycling?
- Choline uptake into the presynaptic terminal
2. Choline + AcCoA – ChAT–> ACh + CoA –> ACh into vesicles
What is ChAT?
choline acetyltransferase
Draw the recycling phase
How does Choline get reuptake to the presynaptic terminal?
By a Na+-choline cotransporter
- Na+ comes in too
What converts choline to ACh?
ChAT - choline acetyltransferase
What moves the ACh to the vesicles?
VAChT- vesicle ACh transporter
What stimulates Fatigue of the presynaptic terminal?
High frequency nerve stimulation- depletion of ACh/vesicles
What is Synaptic delay?
the delay between presynaptic depolarization and postsynaptic depolarization (EPP)
What is the “normal” range for synaptic delay?
0.5-3 ms
What is the slowest step of synaptic transmission?
activation of nmAChR
What are the two mechanisms behind Facilitation?
- residual intracellular Ca2+ near presynaptic terminal membrane-> increases P/Q channel activation
- increased Ca2+ influx causes increased ACh release
When does facilitation of the EPP occur?
When intervals of the stimulus are short enough
Between A alpha neuron and Skeletal muscle (SKM), which has a lower Vrest?
SKM Resting potential= -90 mV
Aa neuron= -70mV
Between A alpha neuron and Skeletal muscle (SKM), which has a lower Vthreshold?
Both are equal= -50mV
Between A alpha neuron and Skeletal muscle (SKM), which has a longer Absolute refractory period?
SKM= 3-4 ms
A alpha neuron= 1ms
Between A alpha neuron and Skeletal muscle (SKM), which has a faster conduction velocity?
A alpha neurone= 20-100m/s
SKM= 1 m/s
Why is SKM slower than A alpha neuron in conduction velocity?
because there is no myelination
