Synapses and the NMJ Flashcards
Whats an electrical synapse
Direct contact between two adjacent cells through gap junctions
How are electrical synapses formed?
Via 6 connexins joining to form 1 connexion which lines up with connexion in adjacent membrane to form pore
Where are electrical synapses found? What are their proterties?
Found in glial neurone, Glial glial communication
Also between Cardio myocytes
Fastest form of communication
bidirectional
allow synchronous activity between cells
What type of synapse is found between two neurones?
Chemical Synapse
What are the properties of a chemical synapse?
no direct contact between neurones
unidirectional transport
uses neurotransmitters
Fast but slower than gap junctions
How do chemical synapses work in terms of the presynaptic membrane?
Why is Ca2+ so important?
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
What happens from the release of NT in a chemical synapse?
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
How is the message form a chemical synapse terminated?
Dependant on NT either:
Enzymatic breakdown
Reuptake of NT
How do excitatory ionotropic receptors work?
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
How do inhibitory ionotropic receptors work?
NT release binding conformational change channel opening Cl- ion influx hyperpolarization small inhibitory postsynaptic potential
GPCRS
What kind of response does this produce?
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
What is spatial summation?
How can it lead to the generation of an AP
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
What is Temporal Summation
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
What is the NMJ
How is it specialised?
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
What the role of Ca2+ at the NMJ
AP arrives at presynaptic terminal
depolarisation
Ca2+ influx
causes vesicles to fuse with the presynaptic membrane and ACh release via exocytosis
What happens on the post synaptic membrane once ACh has been released at the NMJ?
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
Why is there such a large influx of Na+ at the NMJ
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+
What is the Em of a myocyte
-90mV
How does the large EPP generated result in an action potential
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.
Why does the EPP decay ?
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
What is important about Ca2+ inside myocytes
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
How is Ca2+ released from the sarcoplasmic reticulum?
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
What is the fate of ACh in the NMJ?
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
What is Myasthenia Gravis
Autoimmune condition that targets nAChR’s on the postsynaptic membrane
results in poor synatpic transmission
Symptoms include muscle weakness particularity noticeable around the eyes
How is Myasthenia Gravis treated?
AChE inhibitors means ACh present for longer at NMJ therefore allowing muscle contraction
neostigmine
