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Flashcards in Neuromuscular Junction Deck (53)
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1

Synapses

communication occurs via the release of chemical messengers (neurotransmitters) from presynaptic nerve terminals to act upon receptors on the postsynaptic membrane

2

Neuromuscular junction

synapse between neurone and a skeletal muscle fibre

3

Synaptic transmission at the neuromuscular junction

the release of transmitter onto receptors involves 5 steps, each of which can be affected by drugs and toxins resulting in either an increase or decrease in transmission

4

5 steps of synaptic transmission

1. synthesis of the transmitter from a precursor and an enzyme
2. storage of transmitter
- protect
- package (quanta)
3. transmitter released by vesicular exocytosis
4. activation by binding of transmitter to receptors
5. transmitter reaches inactivating enzyme and there is an uptake of transmitters

5

Drugs can enhance synaptic transmission by

Direct stimulation of post-synaptic receptors by
- the natural transmitter
- analogues
Indirect action via
- increased transmitter release
- inhibition of transmitter removal

6

Drugs can inhibit synaptic transmission by

- blocking synthesis storage or release from the presynaptic neurone
- blocking postsynaptic receptors

7

Drugs acting directly on receptors (types)

agonists and antagonists

8

Agonists

- drugs, hormones or transmitters which bind to specific receptors and initiate a conformational change in the receptor resulting in a biological response
- affinity and efficacy

9

Affinity

the ability of agonists to bind to receptors

10

Efficacy

the ability of an agonist, once bound to a receptor, to initiate a biological response

11

What is the neurotranmitter at the NMJ?

acetylcholine

12

Activation of receptors by agonists

- an agonist binds with a receptor to produce an agonist/receptor complex
- the receptor is ligand-specific and so is like a 'lock and key'

13

Binding step (agonists)

Agonist + receptor
- affinity

14

Activation step (agonists)

complex --> response
- efficacy

15

Antagonists

Antagonist + receptor -> complex
- affinity
- antagonists bind to receptors but do not activate them
- possess affinity but lack efficacy
- antagonists block receptor activation by agonists

16

Competitive nicotinic receptor antagonists

competes with the agonist for the agonist binding site on the receptor; block is reversed by the increase in agonist concentration

17

How are synapses classified?

- according to the transmitter released from the presynaptic neurone
- for synapses where the presynaptic neurone synthesises and released ACh transmission = cholinergic
- receptors which ACh acts on are called cholinoceptors

18

Types of cholinoceptors

Nicotinic
- activated by ACh or nicotine but not muscarine
Murcarinic
- activated by ACh or muscarine (fungal alkaloid( but not nicotine

19

What is the nicotinic ACh receptor?

a transmitter-gated ion channel

20

Transmitter-gated ion channels

- integral ion channel
- agonist binding to the receptor induces a rapid confrormational change to open the channel
- the channel is selective for certain ions
- signalling is extremely rapid (milliseconds)
- consist of seperate protein subunits that form a central, ion conducting, channel
- allow rapid changes in the permeability of the membrane to certain ions
- rapidly alter membrane potential

21

What does ACh released from a vesicle cause?

- a miniature endplate potential (MEPP)
- it activates many nicotinic ACh receptors
- upon activation the associated nicotinic cation channels open and Na ions flux into the muscle fibre to cause a local depolarisation at the endplate region

22

Synaptic transmission at the neuromuscular junction

- motor nerve stimulation causes synchronous release of many vesicles; summation of mepps to produce an epp
- membrane potential is negative
- MEPP molecules depolarise past the threshold
- this causes voltage gates Na channels to open

23

Quantal content

- number of vesicles/stimulus
- QC = (mean EPP amplitude (mV) / (mean MEPP amplitude (mV)
- each quanta gives rise to a miniature end plate potential (mepp) via activation of nicotinic ACh receptors

24

When do mepps occur?

spontaneously

25

When do epps occur?

in response to a motor nerve stimulation

26

What happens when mepps summate to give an epp?

Initiates an action potential which causes muscle contraction

27

Cholinergic transmission and the NMJ

- choline acetyl transferase (CAT) synthesises ACh from precursors choline and AcE A from mitochondria
- Re-uptake of choline is Na dependent and blocked competitively by hemicholinium 3
- there will be less ACh in each vessicle
- amplitude f the epp and mepp both decrease

28

Tetrodotoxin (TTX)

- blocks Na channels (no action potential, no release, no EPP)

29

Conotoxin

- blocks voltage-gated Ca channels
- a decrease in calcium influx decreases the release
- the epp amplitude decreases, no change in mepp amplitude
- decreased quantal content

30

Dendrotoxin

- blocks voltage-gated K channels
- prolonged action potential
- increased calcium influx causes an increase in release
- increased epp amplitude
- no change in mepp amplitude
- increased quantal content