Mechanism of Neurotransmitter Release and Reuptake

It is a tetra-helix of extreme stability that allows the fusion of vsicle membrane with target membrane. It is composed of the v-SNARE synaptobrevin or VAMP, and the t-SNARES syntaxin (1 helix) and SNAP-25 (2 helices)

The toxins cause cleavage of constituent proteins (botulinum toxin attacks each of the three SNARE proteins, whereas the tetanus toxin only cleaves the extracellular alpha helix of synaptobrevin)

Its highly stable interactions between its alpha helices makes up for the fact that displacing of water molecules between the vesicle and the target in the pre-synaptic membrane, which is necessary for vesicle fusion, is not favorable (water’s interactions with the phospholipids heads of the membrane are very strong)

Because the Na+ concentration in the cytoplasm is significant and [Ca2+] is very low, [Ca2+] allows for a less frequent release of NT and spontaneous release of NT is kept at a minimum.

Through VGluT, an antiport that uses the favorable H+ transport out of the vesicle to pump the unfavorable NT transport inside the vesicle

It is a GTPase on the vesicle membrane and is reponsible for memberane docking of vesicle.

They are the hotspots near voltage gated Ca2+ channels where [Ca2+] is high

1) Voltage-gated Ca2+ open in a graded fashion to the amount of depolarization in the presynaptic axon terminal
2) Ca2+-mediated vesicle fusion with the axon (of docked and primed vesicles)
3) the NT contents of the vesicles are release and diffuse through the synaptic cleft (takes 1 ms)

a guanine-factor in the membrane promotes the exchange of GDP to GTP in rab3. When GTP-bound, rab3's affinity to the rab effector proteins in the plasma membrane, bringing interlocking SNARE protins in the 2 membranes closer together. Rab3 has its GTP hydrolyzed to GDP

GDP dissociation inhibitor pulls rab3-GDP and stores it in an inactive form. It has 3 roles:
1) maintains a reserve pool of GDP bound-Rab3
2)transports the reserve pool to the synaptic membrane where GTP replaces GDP
3)pulls Rab3 back into the reserve pool once GTP is hydrolyzed

1) the depolarizations at the synapse of interest were at least .4mV in height or were some multiple of this
2) effects of drugs such as curare and prostigmine showed that each mEPP was generated by a packet of acetylcholine since amplitude of the depolarizations was affected by these drugs
3) m=EPP/mEPP=ln (N/n0)
4) one mEPP (.4mV) would take 4000 molecules of acetylcholine and modern studies indicate that something close to 5000 molecules of NT are found in a single vesicle

the neuromuscular junction: the synapse between a motor neuron's axon and a muscle fiber

X-linked mental retardation accompanied by epileptic seizures

Synaptotagmin

It bridges the distance between the membrane of a synaptic vesicle and the plasma membrane of an axon terminal.

Curare is a nicotinic agonist that works postsynaptically (does not change m or mEPP, but affects EPP). Because it does not affect frequency of the depolarizations, it has a postsynaptic effect.

Prostigmine is an antagonist of acetylcholinerase which degrades the NT acetycholine in the synaptic cleft. This drug therefore increases amplitude of EPP, but still does not increase frequency of depolarizations, indicating again that it works postsynaptically.

n_x=N(m^x/x!)e^-m

Where:
n_x= number of times you see a certain quanta in a number of trials
N=total number of trials
m=mean number of mEPPs/EPP

Ca2+ is bound on synaptotagmins “2 arms at its C terminal” called the C2 domains that induce a change in the shape of the protein. These C2 domains are inserted into the plasma membrane, inducing fusion of vesicle membrane and the plasma membrane. Synaptotagmin therefore acts as a clamp of the SNARE complex and prevents the complex’s alpha helices from binding with one another.

Yes

m=ln(N/n0)

1) clathrin-mediated endocytosis in terminals that are repeatedly depolarized
2) kiss and run- the vesicle fuses to release its contents and then buds back off for immediate recycling
3) bulk endozytosis of membrane builds up after a long period of over-activity in the axon terminal during a high rate of action potentials for an extended period of time

The height of the mEPP stays the same, while m changes which also affects the height of the EPP

1) Recognition of the membrane elements to be captured by endocytosis (by cargo receptors)
2) Clathrin units (triskelia) binds to the cargo receptors by interacting with an adaptor protein called adaptin
3) Addition of triskelia produces a vesicle still attached to the plasma membrane until the protein dynamin pinches off the clathrin coated vesicle
4) Clathrin quickly dissociates to produce a naked besicle

The mutation of dynamin prevents the protein from pinching off the clathrin-coated vesicle. As a result of this mutation, the surface area of the axon terminal increases quickly and dramatically, which can be detected as a massive increase in membrane capacitance

It is a temperature-sensitive mutation in dynamin. As T is raised, dynamin stops working and vesicles accumulate, halting neurotransmission.