NAS L7

Question 1

To get a proper muscle contraction what do you need in terms of action potentials and their frequency? Is this the same as temporal and spatial summation?

Answer 1

Need multiple events/action potentials in close proximity i.e. high frequency to get sustained muscle contraction as you get summation.
Increased frequency –> sustained contraction.
Different from spatial or temporal summation

Question 2

What is a NMJ?

Answer 2

Specialised synapse between motor neuron and muscle cell, fine tuned for rapid and reliable NTmission.

Question 3

What is the role of Ca2 in excitation-contraction coupling in the NMJ?

Answer 3

Role of Ca2+: Ca2+ conc inside is lower than outside. Action potential in presynapse, leads to depolarisation opening of Ca2+ channels and Ca enters presynapse, fusion of vesicles with presynaptic membrane and Ach release by exocytosis. Ca2+ sensor is synaptotagmin. Change in conformation on Ca binding triggers the vesicle fusion. Ach binds to nAchRs on post synaptic membrane - ionotropic/ligand gated ion channel

Question 4

What receptors does Ach bind to on post-synaptic membrane in NMJ?

Answer 4

nAchRs

Question 5

What are the glutamate receptor subtypes (not NMJ)?

Answer 5

AMPA, NMDA, kainate

Question 6

In contrast to brain how much NT and vesicles you get?

Answer 6

You get LOADS of NT and LOADS vesicles.

Question 7

What takes choline back up into pre-synaptic terminal?

Answer 7

Choline carrier

Question 8

What disease affects the NMJ?

Answer 8

Myesthenia gravis - autoimmune disease of nAchRs - reduced number at NMJ. Treatment is AchE inhibitors to prolong the signal. First firing event is ok but decay after firing even as failure of NMJ so muscle tension is decreased

Question 9

What is the endplate resting potential?

Answer 9

-90mV

Question 10

How is the post-synaptic membrane/muscle functionally specialised to ensure the synapse is going to work in the NMJ?

Answer 10

Junctional folds of post-membrane, high density of nAchRs and Na channels deeper in folds. So you get larger depolarisation than you would see in CNS.

Question 11

What 2 receptors are found on post-synaptic membrane in NMJ?

Answer 11

nAchRs and Na+ receptors

Question 12

What is the special name for post synaptic membrane in NMJ?

Answer 12

Motor endplate

Question 13

How is the signal terminated in the NMJ (NT)?

Answer 13

AChE enzyme breaks down Ach into choline and CoA?

Question 14

How much mV worth of depolarisation do you in the NMJ compared to the brain?

Answer 14

From -90mV to -20mV so 70mV worth of depolarisation

Question 15

What does end plate potential go to after depolarisation?

Answer 15

-20mV

Question 16

What does the end plate potential initiate in the muscle?

Answer 16

An action potential.
Ach binds to nAchRs. Channel opens, pearmeable to Na and K. Em of muscle -90mV. Na influx and K efflux leads to end plate potential of -20mV.

Question 17

What fades and what keeps going into muscle after depolarisation and triggering of action potential?

Answer 17

EPP fades but action potential keeps going into muscle

Question 18

What are EPP and action potential?

Answer 18

Different things:
-EPP decays as it move aways from end plate and is the one to initiate the action potential. EPP is generated by ligand gated channels leading to the opening of v.g. channels that give the action potential EPP is very large, many Ach vesicles released and high density of nAchRs. So threshold for action potential is easily passed, high density of .g. Na channels at the endplate.

Question 19

Describe events that happen when action potential travels down the t-tubule

Answer 19

Action potential propagates along the muscle and invades T tubule system, allowing transmission of AP deep into muscle fibre to separate myofibrils.
Depolarisation travels down t-tubule –> have DHP – dihydropyridine receptors / L-type v.g. Ca channel. This is tethered to ryanodine receptor, changes conformation change and then Ca2+ released from SR into intracellular space –> contraction. During repolarisation you get replugging of receptor on SR and Ca uptaken into SR again.