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Synaptic Transmission
9/12/11 Second Lecture
36
Medical
Graduate
09/14/2011

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Term
Name 3 types of cells that synapses occur between
Definition
1. two neurons

2. Presynaptic neuron and postsynaptic target (ex. muscle cell)

3. Presynaptic sensory cell and postsynaptic neuron
Term
Describe the differences between electrical and chemical transmission
Definition
1. Electrical has direct cell-cell contact via connexons, chemical invovles release into the synaptic cleft

2. Electrical has cytoplasmic continuity, chemical does not

3. No synaptic delay in electrical, there is one in chemical

4. Electrical is bi directional, chemical is uni directional
Term
What is the neurotransmitter involved in neuromuscular junctions?
Definition
Acetylcholine
Term
Describe the steps in chemical transmission that involve the presynaptic cell
Definition
1. ACh (transmitter) is stored in vesicles
2. Docking of the vesicles
3. Depolarization of the cell
4. Ca influx via voltage gated ion channels
5. Vesicle fusion
6. Exocytosis
Term
How can you determine which cells are the pre and post synaptic on a slide?
Definition
Presynaptic cells have an abundance of vesicles visible in them as well as many mitochondria present
Term
How can you determine if the junction you are looking at on a slide is neuron-neuron or neuron-muscle?
Definition
In a neuron-neuron synapse, the membrane appears as a relative flat line. In neuron-muscle synapses there are folds in the membrane that go into the muscle cell
Term
Describe the steps in chemical transmission that involve the post synaptic cell
Definition
1. Activation of transmitter receptors (nACh for ACh transmitter)
2. Depolarization of cell
3. Opening of ion channels
4. Ion influx (usually Ca)
5. Ca triggered release of Ca by sarcoplasmic reticulum
6. Inactivation of transmitter
Term
What are the two major families of transmitters and describe differences in their creation and packaging.
Definition
1. small molecules vs. peptides and polypeptides
2. Small molecules are synthesized locally, whereas peptides are synthesized remotely and transported to the terminal
3. Small molecules are in small vesicles, peptides are in large dense core vesicles
Term
What 2 compounds are acetylcholine synthesized from?
Definition
Acetate and choline. Synthesizes is enzyme mediated.
Term
What is the energy source that vesicles use to drive the filling of neurotransmitters?
Definition
ATP is utilized to create a proton gradient in the vesicle (vesicle acidification). The energy of this gradient is then harnessed to drive the filling of neurotransmitters.

Note: Vesicles can also fuse with neurotransmitter filled endosomes to fill
Term
What is the kiss and run process and when does it happen?
Definition
1. Vesicles dock to the membrane surface
2. During the priming phase, Ca is needed for fusion to occur
3. Before Ca influx and fusion occurs, the vesicle breaks off the membrane and returns to the cytoplasm

This process commonly happens when the presynaptic terminal is very active
Term
What proteins are used to mediate docking of the vesicles?
Definition
SNARES (via coil-coil interactions)
Term
What is the role of synaptotagmin and how does it accomplish this? What happens if you disable synaptotagmin?
Definition
1. Membrane protein that mediates fusion of the vesicle and calcium release

2. Does this by sensing calcium levels

3. Without synaptotagmin, you get binding to the membrane but no fusion and NT release
Term
How does tetanus toxin work?
Definition
It affects SNARES to block the function of inhibitory connections, leading to rigidity and convulsions
Term
How does Botulin toxin work?
Definition
Affects SNARES at the neuromuscular junction stopping muscle activity alltogether
Term
What is an EPSP and how do they govern signal conduction?
Definition
1. EPSP is an excitatory postsynaptic potential caused by ACh locally, or a voltage change at the postsynaptic cell

2. If the EPSP reaches threshold for ion channels to open and Ca influx to occur, a signal will be transduced across the synaptic cleft into the postsynaptic cell
Term
What 3 factors affect EPSP amplitude?
Definition
1. Quantity of NT released
2. Quantity of NT that reaches receptors
3. Number of activated receptors
Term
What are miniature EPSP's and why do they occur?
Definition
small transmembrane voltage changes that are unassociated with presynaptic stimulation. They are due to the spontaneous release of a single vesicle.
Term
What is meant by "Postsynaptic potentials can be excitatory or inhibitory"?
Definition
Excitatory - increase the probability of an action potential

Inhibitory - decrease the probability of an action potential
Term
What 3 factors determine whether a transmitter depolarizes or hyperpolarizes the postsynaptic cell?
Definition
1. Resting potential of the post membrane
2. Ion selectivity of the channels that open
3. Electrochemical driving force for that ion (combination of outside concentration vs. inside concentration as well as resting voltage)
Term
Give estimates of the intracellular concentration, extracellular concentration, and nernst potentials for Na
Definition
Intra: 12 Extra: 140 Nernst: 66
Term
Give estimates of the intracellular concentration, extracellular concentration, and nernst potentials for K
Definition
intra: 140 extra: 4 nernst: -93
Term
Give estimates of the intracellular concentration, extracellular concentration, and nernst potentials for Ca
Definition
intra: 10^-4 mM extra: 2.5 nernst: 135
Term
Give estimates of the intracellular concentration, extracellular concentration, and nernst potentials for Cl
Definition
intra: 2.5-50 extra: 115 nernst: -42
Term
What are the two families of receptors and do they support fast or slow EPSP?
Definition
1. Ionotropic - fast

2. Metabolic - slow
Term
What are the 3 methods of transmitter inactivation?
Definition
1. Diffusion out of cleft (slow)

2. Hydrolysis of the transmitter in the cleft

3. Re-uptake of transmitter into presynaptic cell
Term
How is acetylcholine inactivated?
Definition
Acetylcholinesterase cleaves ACh back into its original acetate and choline components, which are taken back up by the presynaptic cell by a sodium ion driven pump
Term
Describe the reuptake of dopamine and how this is affected by cocaine
Definition
Dopamine is not degraded in the cleft, but taken up in its NT state by a pump harnessing the energy of the sodium gradient. Cocaine blocks the activity of this pump, leaving the synaptic cleft flooded with dopamine.
Term
What class of compounds blocks the reuptake of Serotonin and give an example of one
Definition
SSRIs (Selective Serotonin Reuptake Inhibitors)

Prozac
Term
Name 5 examples of transmitters that are inactivated by reuptake mechanisms
Definition
1. Dopamine
2. Serotonin
3. GABA
4. Glycine
5. Glutamate
Term
What is the main cause of Myasthenia Gravis and what are the symptoms?
Definition
1. An autoimmune disease against nAChR leading to a decrease in their number at the neuromuscular juncion

2. Patients become very tired or weak after little to moderate activity (ex. cant speak for long periods of time, droopy eyelids, etc.)
Also a decrease in EMG signal is observed with prolonged activity
Term
What toxin is used to isolate and study nAChRs?
Definition
Bungarotoxin
Term
What is the mechanism of nAChR decrease in MG?
Definition
1. Antibodies compete for and bind to the nAChRs
2. Antibodies cross link, serving as a signal for endocytosis
3. Endocytosed receptors get degraded
Term
What are AChE Inhibitors and what effect do they have on signal transduction?
Definition
1. Acetylcholinesterase inhibitors

2. By stopping ACh from being degraded, an increased quantity of them exist in the synapse, leading to increased chance of the EPSPs crossing threshold for signal transduction
Term
What is facilitation and what causes it?
Definition
1. Facilitation is a transient increase in synaptic strength when two or more action potentials occur in close succession (leads to an increase in EPSP amplitude)

2. The transient increase in [Ca] in the presynaptic terminal after the first stimulation leads to an increase in vesicle fusion and release in subsequent stimulations
Term
What is heterosynaptic potentiation?
Definition
When one synapse's activity is altered by that of another synapse

ex. if you have both a calcium and a sodium receptor and both are activated, the resulting electrical signal in the post synaptic cell is a reflection of the sum of the two synapses' signals
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