Chapter 5: Synaptic Transmission

What is botulinum toxin?

Botulinum toxin prevents release of NT from motor neurons. It severs SNARE proteins.

What is clathrin?

Clathrin is a soluble protein that assembles into a soccer-ball like structure. In the context of cells, there are adapter proteins that trap the clathrin into the membrane that then leads to the formation of the soccer ball.

What's the problem with vesicle addition into the synaptic cleft?

If vesicles fuse to the presynaptic membrane, it will just get bigger and bigger up until it starts to balloon.

What is synapsin-P?

It's synapsin phorsphorylated by Ca2+/CaM-dep PK, and it releases vesicles from the cytoskeleton.

What's connexin?

It's the protein that makes connexons, or the aqueous channels that allow water soluble molecules that are smaller than 1000 Da to pass through.

What are they two types of synapses?

There are electrical and electrical synapses.

What is an important feature of the electrical synapse?

There is a feature called the gap junction between cells. The presynaptic cells are structurally indistinguishable from the post-synaptic cell.

What is the function of electrical synapses?

They allow the rapid transmission of electrical signal from cell to cell. There's much more of a direct pathway, as opposed to having to modify the message.

What are SNARES?

They are SNAP receptors. Snap receptors are soluble, NSF-associated protein. (NSF is NEM-sensitive fusion protein)

What is the structure of connexons? What are they?

They are integrated membrane proteins that are made of sibunits.

What are MEPPs?

They are spontaneous potentials that mimic action potentials. They are eliminated by treatment with curare.

What are chemical synapses?

They have distinct features. The presynaptic cell is distinguished with EM or light microscopy by the indication of synaptic vesicles. The postsynaptic cell has neurotransmitter receptors. A synaptic cleft separates pre and post synaptic cells.

Which of the following is an accepted criterion for defining a molecule to be a neurotransmitter? a. It must be present in the presynaptic terminal. b. It must be released in response to presynaptic electrical activity. c. It must exert an effect on the postsynaptic cell. d. All of the above e. None of the above

d. All of the above

Gap junctions may exhibit all of the following features except for the ability to a. pass small metabolites, including some second messengers. b. pass electrical current bidirectionally. c. pass electrical current unidirectionally. d. amplify small incoming electrical signals into large regenerative potentials. e. synchronize the activity of populations of nerve cells.

d. amplify small incoming electrical signals into large regenerative potentials.

Activating end plate acetylcholine receptor channels produces 0 current at 0 mV, but is still able to elicit action potentials in muscle fibers because a. the depolarization occurs so quickly that the membrane potential goes far positive to 0 mV and produces an overshooting action potential. b. there are enough acetylcholine receptors to propagate the action potential along the length of the muscle fiber. c. the receptor is also permeable to calcium, which binds to other channels to elicit action potentials. d. depolarization of the membrane to 0 mV is sufficient to bring nearby membrane regions, which contain voltage-gated sodium channels, to threshold. e. None of the above; acetylcholine does not elicit muscle action potentials

d. depolarization of the membrane to 0 mV is sufficient to bring nearby membrane regions, which contain voltage-gated sodium channels, to threshold.

What was the drive home point about a MEPP? What is so special about it? The overall conclusion of the experiment?

A MEPP represents the resopnse of the muscle cell to a quantum of released NT. The synaptic vesicles carried calcium, located within 40 nm of calcium channels.

Explain the synapse of a chemical message.

An action potential invades the presynaptic terminal. The depolarization of the presynaptic terminal causes the opening of the calcium channels, and they rush it. The calcium causes the vesicle to fuse with the presynaptic membrane, and the transmitter is released into the synaptic cleft. They diffuse across the synaptic cleft. Some of them find to a receptor on the postsynaptic membrane, either opening or closing them. It changes the conductance membrane of the postsynaptic membrane that sometimes leads to postsynaptic potential. The neurotransmitter is taken by glial uptake or degradated with enzymes.

What do electrical synapses allow for?

Electrical synapses allow for synchronization of cellular activity in electrically coupled cells. For example, when neuron 1 fires, neuron 2 fires.

What is the role of calcium in the neurotransmitter secretion?

Fatt & Katz's work implied that calcium was important in synaptic transmission. Axon terminals contain v-g calcium channels as evidence by: observation of APs in axon terminals, even when treated with TTX (blocks sodium channels) The voltage clamp revealed an inward of current. If calcium was blocked by cadmium, the post-synaptic cell failed to respond in presence of cadmium.

Who are Fatt and Katz? What were they working on? Why?

Fatt and Katz were trying to know how the chemical synapses work. They worked on the neuromuscular junction because the it was more accessible and because muscle is excitable and can be recorded. However, sometimes the muscle would synapse without input which would cause skewed data. This was solved with lowering the Ca+ and using curare.

Do cells ever touch each other? What links them?

No, that's why we say that there's a thing called a gap junction. Channels called connexons link them together to allow the ionic current through both cells.

What is synapsin?

Synapsin is a calcium sensitive protein that tethers the vesicle to the cytoskeleton.

Waht is synaptotagmin?

Synaptotagamin binds Ca2+ and inserts it into the membrane. It binds together SNAREs.

What's the solution to the ballooning of vesicles on the synaptic cleft? How was it discovered?

The idea is that the membrane is recovered through endocytosis. This was discovered by the finding of HRP in coated vesicles, then early endosomes, then synaptic vesicles. It takes about a minute.

What was observed during their experiment?

The results showed that you would get a stimulation of motor neuron in the presence of calcium. Calcium would rush in, depolarizing the cell membrane past the threshhold, and then resulting in an action potential. There was about a 2ms delay.

How does calcium cause vesicle fusion?

This is not completely, 100% understood. But we believe that it's because of interaction with specific calcium binding proteins on the vesicle, presynaptic membrane, or both.

True or false: Depolarization of presynaptic neuron is insufficient to generate postsynaptic response

True

True or false: Injection of calcium buffers into the presynaptic neuron prevents post-synaptic response

True

True or false: A rise in intracellular calcium is both necessary AND sufficient for NT release, and by extension, synaptic transmission.

True.

True or false: Injecting calcium causes the NT release

True. Demonstrating that elevation of intracellular calcium is sufficient to cause vesicle fusion. Depolarization is not, strictly speaking, necessary.

What was the general trend of number of vesicles fusing and number of quanta released?

Under normal circumstances, it's pretty close to about one to one.

What happens if you stimulate the neuron in absence of extracellular calcium?

You see small EPPS, or small end plate potentials. They occur spontaneously and are about 0.05.

The protein that is thought to cross-link vesicles to actin to form a reserve vesicle pool is called a. synapsin. b. synaptotagmin. c. synaptobrevin. d. synaptophysin. e. snap 25.

a. synapsin.

Listed below are the individual events that make up chemical synaptic transmission. Diffusion of transmitter across the synaptic cleft Depolarization of the presynaptic terminal Vesicle fusion with plasma membrane Opening of voltage-gated ion channels Activation of presynaptic, calcium-sensitive proteins. Which of the following is the correct sequence of these events? a. 1; 2; 3; 4; 5 b. 2; 4; 5; 3; 1 c. 2; 5; 4; 3; 1 d. 5; 4; 2; 3; 1 e. 1; 2; 4; 5; 3

b. 2; 4; 5; 3; 1

When a muscle fiber is held at a voltage of 0 mV at the neuromuscular end plate, acetylcholine no longer produces a current because a. the acetylcholine receptor channels all close instantly at 0 mV. b. an influx of sodium is balanced by an equal efflux of potassium. c. the membrane conductance for each permeant ion is 0 at 0 mV. d. at 0 mV, the potassium ions lodge in the receptor channel and block the influx of sodium. e. the Nernst potentials for both sodium and potassium are 0 mV in muscle fibers.

b. an influx of sodium is balanced by an equal efflux of potassium.

Black widow spider venom is thought to disrupt the functioning of nerve terminals by a. proteolytic cleavage of SNARE proteins. b. circumventing the calcium-regulatory step of exocytosis to promote massive exocytosis. c. binding to all molecules of synapsin, synaptotagmin, and synaptophysin and thereby preventing their normal functioning. d. punching holes in vesicles and thereby causing release of their contents into the cytosol. e. blocking calcium channels.

b. circumventing the calcium-regulatory step of exocytosis to promote massive exocytosis.

The capability of a nerve terminal to rapidly and dramatically produce very large changes in calcium levels is most dependent on the a. presence of calcium-selective ion channels. b. enormous gradient of calcium across the membrane. c. fact that calcium is a positively charged ion. d. fact that calcium is a divalent cation. e. All of the above are essential for producing large, rapid concentration changes.

b. enormous gradient of calcium across the membrane.

The two main families of neurotransmitter receptors are _______ and _______. a. ligand-gated; ion-gated b. ionotropic; metabotropic c. voltage-gated; voltage-modulated d. cationic; anionic e. excitatory; inhibitory

b. ionotropic; metabotropic

The differential release of small, clear vesicles, versus large, dense-core vesicles, is best explained by a. biophysical differences in the vesicles' lipids that allow for easier fusion of small vesicles. b. a more sensitive calcium-release mechanism on the dense-core vesicles. c. a more delocalized calcium signal generated by intense neural stimulation. d. the presence of novel fusion proteins on the dense core vesicles that bind neuropeptides. e. All of the above

c. a more delocalized calcium signal generated by intense neural stimulation.

SNARE proteins participate in vesicle exocytosis by a. forming a protein coat that maintains the vesicle's integrity. b. binding calcium and then forming a pore into the vesicle. c. forming a protein complex that pulls the vesicle membrane against the plasma membrane. d. linking calcium channels to exocytotic fusion sites. e. pushing vesicles from the reserve pool into the docked pool.

c. forming a protein complex that pulls the vesicle membrane against the plasma membrane.

Gap junctions (electrical synapses) a. are found only in a few species of animals. b. are far more numerous than chemical synapses. c. have larger pores than voltage-gated ion channels. d. are found only where there are large gaps between nerve cells. e. are used to pass chemical neurotransmitters.

c. have larger pores than voltage-gated ion channels.

Compared with normals, the decrease in quantal size observed in familial infantile myasthenia would be most consistent with a. fewer calcium channels in the presynaptic terminals. b. a greater rate of spontaneous exocytosis depleting the size of the vesicle pool. c. smaller synaptic vesicles. d. a change in the sensitivity of the calcium release mechanism. e. a loss of all ACh receptors at the neuromuscular junction.

c. smaller synaptic vesicles.

The most important factor determining whether a receptor-operated ion channel is inhibitory or excitatory is a. the ligand-binding properties of the receptor. b. whether the permeant ion is positively or negatively charged. c. whether the permeant ion's reversal potential is positive or negative. d. whether the permeant ion's reversal potential is positive or negative to threshold. e. None of the above

d. whether the permeant ion's reversal potential is positive or negative to threshold.

Which of the following experiments would indicate a role for calcium in transmitter secretion? a. Observation of presynaptic depolarizing currents after blockade of sodium channels b. Voltage clamp experiments showing voltage-gated calcium channels in the presynaptic terminal c. Induction of transmitter release by injection of calcium into the presynaptic terminal d. Blockade of transmitter release by injection of calcium buffer into the presynaptic terminal e. All of the above

e. All of the above

In tracking recycling of synaptic vesicles, using HRP as a vesicle marker, the observed sequence of movements of HRP was a. Endosome, coated vesicle, vesicle reserve pool b. Vesicle reserve pool, coated vesicle, endosome c. Endosome, vesicle reserve pool, coated vesicle d. Coated vesicle, vesicle reserve pool, endosome e. Coated vesicle, endosome, vesicle reserve pool

e. Coated vesicle, endosome, vesicle reserve pool

Which of the following statements about postsynaptic currents at the neuromuscular end plate is false? a. Depolarizing currents can be recorded from outside-out patches of postsynaptic membrane. b. Individual channels tend to stay open for no more than a few msec. c. Acetylcholine can induce openings of ligand-gated ion channels. d. The end plate potential is due to the opening of thousands or millions of channels. e. The end plate channels show a regenerative opening pattern that propagates an action potential along the length of the muscle fiber.

e. The end plate channels show a regenerative opening pattern that propagates an action potential along the length of the muscle fiber.

To date, which of the following is not part of the experimental evidence favoring the vesicular release hypothesis of neurotransmission? a. Fixed size of MEPPs b. Quantized distribution of events occurring at the neuromuscular junction c. Visualization of synaptic vesicles using electron microscopy d. Correspondence between a vesicle's acetylcholine content and MEPP size e. Visualization of acetylcholine molecules diffusing out of the neck of the membrane-fused vesicle

e. Visualization of acetylcholine molecules diffusing out of the neck of the membrane-fused vesicle

Miniature end-plate potentials, or MEPPs, are produced a. at miniature end-plates. b. by the smallest axons. c. in response to weak stimuli. d. by the smallest neurotransmitters. e. by spontaneous release of neurotransmitter.

e. by spontaneous release of neurotransmitter.