signal transduction at the neuromuscular junction - pre-junctional events

Question 1

What speed can action potentials travel at?

Answer 1

Up to 120 meters per second

Question 2

what is the result of an action potential?

Answer 2

triggers the release of neurotransmitters at the nerve terminal

Question 3

what is neural communication?

Answer 3

neurotransmitters carry the signal across the synaptic cleft (the gap between the neurone and the post-synaptic effector cell)
the neurotransmitters acting on receptors on the post-synaptic membrane can cause either, excitation or inhibition

Question 4

what is neural communication in the human brain

Answer 4

there are 100 billion neurones, many with more than 1000 synapses resulting in 100 trillion interconnections

Question 5

what is neural communication in the skeletal neuromuscular junction

Answer 5

an ideal model for understanding fast neuronal information transfer

Question 6

what is the synapse

Answer 6

where communication occurs via the release of chemical messengers - neurotransmitters

Question 7

what is neurotransmitter release

Answer 7

released from presynaptic nerve terminals to act upon receptors on the postsynaptic membrane
released via exocytosis in the presence of receptors on the postsynaptic membrane

Question 8

what is the neuromuscular junction

Answer 8

the synapse between a neuron and a skeletal muscle fibre
contains nicotinic acetylcholine receptors

Question 9

what is synaptic transmission

Answer 9

the release of neurotransmitter onto receptors
involves 5 different steps - each step can be influenced by drugs and toxins resulting in either an increase or, a decrease of transmission
1) synthesis
2) storage
3) release
4) activation
5) inactivation

Question 10

synaptic transmission - synthesis

Answer 10

chemical precursors, acetyl CoA and choline, are used to synthesise acetylcholine by choline acetyl transferase (CAT)

Question 11

synaptic transmission - storage

Answer 11

acetylcholine is stored and packaged in vesicles for protection
packaged as quanta

Question 12

synaptic transmission - release

Answer 12

released via exocytosis due to the action potential and increase in Ca2+ ion concentration

Question 13

synaptic transmission - activation

Answer 13

acetylcholine binds to receptors on the post-synaptic membrane causing a conformational change leading to cellular response

Question 14

synaptic transmission - inactivation

Answer 14

acetylcholinesterase enzymes inactivate acetylcholine by breaking it down to acetate and choline.
choline returns to the presynaptic cell

Question 15

enhancement of synaptic transmission by drugs

Answer 15

1) direct stimulation of post-synaptic receptors by
a) the natural transmitter - synthetic transmitter - agonist
b) analogues - carbachol - structural analogue of acetylcholine which is not hydrolysed by cholinesterases
2) indirect action via
a) increased transmitter release
b) inhibition of transmitter removal - inhibition of acetylcholinesterase

Question 16

inhibition of synaptic transmission by drugs

Answer 16

1) blocking synthesis by enzyme antagonist
blocking storage
blocking release from the presynaptic neurone by Ca2+ channel blockers
2) blocking postsynaptic receptors

Question 17

agonists - basic

Answer 17

activate receptor by causing a conformational change

Question 18

antagonists - basic

Answer 18

block the action of the agonist

Question 19

what is an agonist?

Answer 19

a drug, hormone, or transmitter which binds to specific receptors and initiate a conformational change in the receptor resulting in a biological response
two important properties of agonists are affinity and efficacy

Question 20

affinity

Answer 20

the ability of an agonist to bind to a receptor

Question 21

efficacy

Answer 21

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

Question 22

activation of receptors by agonists

Answer 22

A+R <> AR <> AR*
A+R = binding step (affinity)
AR = agonist-receptor complex
AR* = activation step (efficacy)

Question 23

what is an antagonist?

Answer 23

antagonists bind to receptors but do not activate them
possess affinity but lack efficacy
block receptor activation by agonists - prevent agonist binding and activating the receptor
B+R <> BR

Question 24

what is a competitive antagonist

Answer 24

competes with the agonist for the “agonist binding site” on the receptor
block is reversible by increasing the agonist concentration

Question 25

what is acetylcholine (Ach)

Answer 25

the neurotransmitter at the neuromuscular junction
cholinergic transmission to cholinoceptors

Question 26

nicotinic cholinoceptors (nAchRs)

Answer 26

activated by acetylcholine or the tobacco alkaloid nicotene but not by muscarine
ligand-gated ion channels

Question 27

muscarinic cholinoceptors

Answer 27

activated by acetylcholine or the fungal alkaloid muscarine but not by nicotene
G-protein coupled receptor

Question 28

transmitter-gated ion channels

Answer 28

e.g. nicotinic
an integral ion channel
agonist binding to the receptor induces a rapid conformational change to open the channel
the channel is selective for certain ions
signalling is extremely rapid (milliseconds)
> agonist binding causes the pore of the channel to open which allows cations (K+, Na+, Ca2+) to enter which causes depolarisation