Synapses and the NMJ

Question 1

Whats an electrical synapse

Answer 1

Direct contact between two adjacent cells through gap junctions

Question 2

How are electrical synapses formed?

Answer 2

Via 6 connexins joining to form 1 connexion which lines up with connexion in adjacent membrane to form pore

Question 3

Where are electrical synapses found? What are their proterties?

Answer 3

Found in glial neurone, Glial glial communication
Also between Cardio myocytes

Fastest form of communication
bidirectional
allow synchronous activity between cells

Question 4

What type of synapse is found between two neurones?

Answer 4

Chemical Synapse

Question 5

What are the properties of a chemical synapse?

Answer 5

no direct contact between neurones
unidirectional transport
uses neurotransmitters
Fast but slower than gap junctions

Question 6

How do chemical synapses work in terms of the presynaptic membrane?
Why is Ca2+ so important?

Answer 6

Action potential arrives in synaptic bouton

depolarisation

opening of VG Ca2+ ion channels

Results in secretory vesicle movement and release of NT via exocytosis into the synaptic cleft

NT release is Ca2+ dependant

Question 7

What happens from the release of NT in a chemical synapse?

Answer 7

Diffusion across synaptic cleft
binds to specific comp receptor
allostery
opening of ion channels

for excitatory NT = Na+ influx and depolarisation

For inhibitory NT= Cl- influx and hyperpolarisation

Question 8

How is the message form a chemical synapse terminated?

Answer 8

Dependant on NT either:
Enzymatic breakdown
Reuptake of NT

Question 9

How do excitatory ionotropic receptors work?

Answer 9

Nt binds usually 2 molecules
conformational change
channel opening
Na+ influx
Depolarisation
generation of a small excitatory postsynaptic potential (EPSP)
If threshold is met lots of Depolar –> AP generated

Question 10

How do inhibitory ionotropic receptors work?

Answer 10

NT release binding 
conformational change
channel opening
Cl- ion influx
hyperpolarization
small inhibitory postsynaptic potential

Question 11

GPCRS

What kind of response does this produce?

Answer 11

NT can also bind to GPCR’s

conformational change in receptor

activation of heterotrimeric g protein GDP-GTP

Dissociation

subunits can go on to activate enzymes 2nd messenger systems or open g protein gated ion channels

Slower longer lasting response

Question 12

What is spatial summation?

How can it lead to the generation of an AP

Answer 12

if one synaptic event occurs some inotropic Na+ ion channels open –> EPSP does’t overcome threshold so no AP generated

Multiple synaptic inputs opening of VG Na+ channels depolarisation–> spatial summation of EPSP’s, additive depolarisation, threshold easily overcome generation of AP

If you have a excitatory and inhibitory event of equal magnitude they can cancel out through spacial summation

Question 13

What is Temporal Summation

Answer 13

summing of EPSP’s at the same synapse as long as they occur in rapid succession
keep adding to each other additive depolarisation until threshold is overcome and an AP is generated

Question 14

What is the NMJ

How is it specialised?

Answer 14

Specialised synapse

Neruomuscular junction
located between a motor neurone and the motor end plate

Presynaptic membrane thousands of vesicles containing ACh

postsynaptic membrane lots of invaginations of the sarcolemma to form junctional folds
increases the SA and the no of nAChR’s and Vg Na+ channels

Question 15

What the role of Ca2+ at the NMJ

Answer 15

AP arrives at presynaptic terminal
depolarisation
Ca2+ influx
causes vesicles to fuse with the presynaptic membrane and ACh release via exocytosis

Question 16

What happens on the post synaptic membrane once ACh has been released at the NMJ?

Answer 16

ACh binds to nACh receptors (2 molecules)
results in conformational change of ionotropic channel resulting in Na+ influx

thousands of ACh molecules and thousands of receptors causes massive depolarisation due to opening of ligand gated Na+ channels

result in Em changing from–90mV up to -20mV

this is known as the end plate potential

Question 17

Why is there such a large influx of Na+ at the NMJ

Answer 17

So many nAChR’s on postsynaptic membrane and loads of ACh released
and
Concentration gradient wants Na+ to enter and there is a larger electrostatic difference across the membrane Em is -90mV
therefore there is a larger ionic driving force acting on Na+

Question 18

What is the Em of a myocyte

Answer 18

-90mV

Question 19

How does the large EPP generated result in an action potential

Answer 19

Huge EPP form -90mV to -20mv due to opening of ligand gated ion channels easily overcomes threshold and therefore voltage gated Na+ ion channels open leading to further depolarisation and the generation of an action potential.

Question 20

Why does the EPP decay ?

Answer 20

there are no nAChR’s away from the end plate thereof must cause AP as there are abundant VG Na+ ion channels on the sarcolemma

Question 21

What is important about Ca2+ inside myocytes

Answer 21

Ca2+ binds to troponin causing a conformational change thus rotating tropomyosin and exposing acting binding sites for myosin heads

I.e. muscle contraction is ca2+ dependant

Question 22

How is Ca2+ released from the sarcoplasmic reticulum?

Answer 22

AP propagates down T-tubule system causing depolarisation of sarcolemma

Affects the DHP (dihydrpyridine) receptor that is tethered to another ryanodine receptor.

Depolarisation results in DHP conformational change and the pulling of ryanodine receptor out of the sarcoplasmic reticulum leading to Ca2+ efflux into sarcoplasm

Question 23

What is the fate of ACh in the NMJ?

Answer 23

ACh broken down by acetylcholinesterase breaks ACh into choline and acetyl groups

Choline taken back up by specific receptors on the presynaptic membrane and recycled

Question 24

What is Myasthenia Gravis

Answer 24

Autoimmune condition that targets nAChR’s on the postsynaptic membrane
results in poor synatpic transmission

Symptoms include muscle weakness particularity noticeable around the eyes

Question 25

How is Myasthenia Gravis treated?

Answer 25

AChE inhibitors means ACh present for longer at NMJ therefore allowing muscle contraction

neostigmine