Exam1Lec4Synthesis,Storage,andReleaseofNeuro

Question 1

What are gap junctions?

Answer 1

physical/direct connections that allow electrical coupling b/w 2 neurons

all cells have this except skeletal muscles dont have this

Question 2

What are chemical synapses?

Answer 2

where neurotransmitters are released by the pre-synaptic cell via exocytosis

Question 3

What determines whether or not a substance is a neurotransmitter?

Answer 3

4 criteria
1. Synthesized and/or stored in the pre-synaptic cell
2. Targets sites on a post-synaptic receptor
3. Endogenous + exogenous transmitter =same response
4. Has a mechanism to terminate, or deactivate the signal

Question 4

What are the diff types of neurotransmitters?

Answer 4

small molecules, amino acids, peptides, gases,purines, biogenic amines

Question 5

What is exocytosis caused by?

Answer 5

caused by an increase in cytosolic Ca2+ resulting from the depolarization-dependent activation of Ca2+ channels.

Question 6

What is receptor activation?

Answer 6

Neurotransmitter binds (2 mechanism) to postsynaptic receptor, and alters (diverse response) the postsynaptic Vm

Question 7

What is receptor inactivation (removal)?

Answer 7

Transmitters are removed from the synaptic cleft primarily through three mechanisms

Question 8

What is the order of synpatic transmission?

transmitting the ap to another cell

slide 6

Answer 8

NT packaged in vesicle > Docking > Priming > Exocytosis > Endocytosis

exocytosis of neurotran from vesicle into synaptic cleft
endocygtisis: membrane from pre-synaptic terminal to recycle more vesivles for neurotrans

Question 9

Explain electrical synapse vs chemical synpase

Answer 9

electrical synapse: Passive communication via the direct electrical coupling of two cells through gap junctions.

chemical synapse:Communication through the release
and binding of molecules known as
neurotransmitters.

Question 10

What are pore forming proteins (connexins) connecting two cells?

Answer 10

Gap junctions (part of electrical synpase)

many indiv connexins make one connexon thats in one side of membrane andanother on the other side. They come together and makes a hemichannel which makes gap junctions.

Question 11

What are the limitations and advantages of electrical synapses?

Answer 11

Advantage: Rapid signal transmission
(electrical and chemical)
Limitation: Postsynaptic = Presynaptic (Identical signal, ie. less plasticity)

Examples: Coupling among retinal cells, cancer cells or heart muscle

Question 12

What are the limitations and advantages of chemical synapses?

Answer 12

Limitation: slower signal transmission
Advantage: postsynpatic signal varies from presynaptic signal

as ca2+ incr, neurotrans incr

Question 13

What are the 6 main types of small molecule neurotransmitters?

Answer 13

1) Acetylcholine
2) Amino Acids
3) Purines
4) Biogenic Amines
5) Gases (NO, CO)
6) Peptides (much larger)

• BDNF and NGF are “neurotransmitter modulators”

Question 14

Amino acid transmitters can be divided into what

Answer 14

Inhibitory: GABA and glycine. (IPSPs, influx of Cl- ions and/or efflux of K+ ions ) DECR LIKELIHOOD OF AP

excitatory: glutamate and to a lesser extent aspartate. (associated primarily with EPSPs) INCR LIKELIHOOD OF AP

GABAergic Drug examples (activates gaba): Phenobarbital, Diazepam, Vigabatrin
Excitatory Drug examples: Antagonists are Ketamine, Riluzole, and MSG is an Agonist

Question 15

What is the most abundant neurotransmitter in the body?

Answer 15

Glutamate (very ubiquitos)

Question 16

What are 5 examples of peptide neurotransmitters?

Answer 16

1. Brain-gut peptides
2. Opiod peptides
3. Pituatary peptides
4. Hypothalamic-releasing peptides
5. Miscellaneous peptides

need to be injected bc digestive tract will cleave them, making them inactive

Question 17

What is the life cycle of a neurotransmitter?

Answer 17

life cycle of neurotransmitters: 1) synthesis, 2) packaging, 3) release, 4) binding, and 5) inactivation

Question 18

Explain the synthesis of catecholamines

Answer 18

We need Tyrosine (from diet or phenylalanine) to turn into L-DOPA, then to turn into Dopamine, then into Norepi, then to Epi

Enzyme to turn L-dopa to dopamine is DOPA decarboxylase

Question 19

What is the precursor for syntheisis of catechilamines and what is the rate limiting enzyme?

Answer 19

Precursor: Tyrosine (phenylalanine is the amino acid that we can get from diet)
Rate limiting: Tyrosine hydroxylase (turns tyrosine to L-dopa)

Question 20

What are the primary catecholamines?

Answer 20

Primary catecholamines include dopamine, epinephrine, and norepinephrine

Question 21

What are 2 ex of H1 antagonitsts (anti-histamines)

Answer 21

Diohenhydramine (lipophilic)
Loratadine/Claritin (lipophobic)

blocks histidine recp=blocks allergic rxns

Question 22

Explain the synthesis of histamine

Answer 22

Histidine to Histamine by Histidine decarb enzyme

Question 23

Explain the synthesis of serotinin

Answer 23

Tryptophan (essential aa found in diet) converts to 5-hydroxytryptophan then turns into 5-HT (serotonin)

Question 24

Low serotonin is associated with what diseases?

Answer 24

Depression, OCD, ADHD

Question 25

Processing of peptide neurotransmitters

Answer 25

Pre-pro peptides are made inside cell, and then transported down axon. Once they reach their target/ pre-synpatic terminal they are converted to active peptide

Question 26

Explain synthesis of small-molecule neurotransmitters

Answer 26

1. Synthesis of enzymes at soma 2. Transport and recycling of enzymes down axon to pre-synaptic terminal 3. Synthesis and packageing of NEUROTRANSMITTERS at PRE-SYNAPTIC TERMINAL 4. Release and diffusion of neurotransmitter (clear-core vesicles) 5. Transport of pre-cursors into terminal

Question 27

Explain synthesis of peptide neurotransmitters

Answer 27

1. Synthesis of both neurotransmitter PRECURSORS (pro-peptide) AND ENZYMES 2. Transmitter + enzymes are packages in Dense core vesicles which bud off golgi. 3. Transport of enzymes and pre-peptide precursors down axon via microtubules 3. Enzymes MODIFY PRE-PEPTIDES to produce ACTIVE peptide neurotransmitters at pre-synaptic terminal 4. Neurotrans diffesee away

Question 28

How are small molecule neurotransmitters packaged?

Answer 28

BY Clear core vesicles: small molecule transmiters (5-HT,ACh) are made at the pre-synaptic nerve terminal. Transmitters are stored in endosomes which then bud off small, clear-core vesicles.

Question 29

How are larger, pro-peptide transmitters packaged?

Answer 29

By Dense-core vesicles: larger,pro-peptide transmittets are made in cell body, *with enzymes packages together in dense-core vesicles.* These bud off golgi and then transported along the axon,

Question 30

What is the membrane fusion machinery responsible for docking and priming of vesicles?

Answer 30

vSNARE =synaptobrevin (botulism target target, many types of SNAREs) and tSNARE (t=target membrane=pre-synaptic terminal) vesicles are docked with pre-synap membrane to be primed and released into pre-synaptic terminal. Docking and release of vesicles and neurotransmitters at pre-synaptic terminal involve V and T snares. ## Footnote V snare is associated with vesicles SNAPs (soluble NSF attachment protein; NSF co-factors)

Question 31

Fusion of vesicles to pre-synaptic membrane is Ca2+ dependent. Explain this

Answer 31

AP triggers incr Ca2+. Synaptotagmin acts ar the putative Ca2+ sensor and has an affinity for binding it. Ca2+ bound to Synaptotagmin induces vesicular and plasma membrane fusion via interaction with SNAP-25

Question 32

Explain how vesicle/neurotransmitter is released by excytosis? | release of a neurotransmitter

Answer 32

1. Fusion of primed vesicles following influx of Ca2+ through activated voltage-gated Ca2+ channels. 2. Synpasin formes complex of vesicles>docking> priming> snares docks vesicle to pre-synaptic membrane 3. synaptotagmin is activated by calcium for vesicular fusion with pre-synaptic membrane. (synaptotagmin senses and binds Ca2+) **Ca2+ & synaptotagmin induces vesicular fusion via interatiction w/ SNAP-25**

Question 33

Explain how a vesicle membrane can be recovered by endocytosis?

Answer 33

Budding occurs with clathrin (initiates endocytosis event by coating membrane) and dynamin acts like a molecular scissor meaning that the vesicle is cleaved by dynamin.

Question 34

what does botulism toxin do?

Answer 34

its neurotoixin that cleaves snares proteins and blocks exocytosis of ACh vesicles ## Footnote causes paralysis of muscle can work at different amino acid sequences of proteins multiple targets: synpatobrevunn, syntaxin, snap-25

Question 35

# mechanism of postsynamotic transmitter binding Explain ligand-gated ion channels (direct gating)

Answer 35

1. Neurotransmitter binds (ex: GABA) 2. Channel opens 3. Ions flow across membrane (Cl goes into cell)

Question 36

# mechanism of postsynamotic transmitter binding Explain G-protein coupled receptors (direct gating)

Answer 36

1. Neurotransmitter binds 2. G-protein is activated 3. G-protein subnunits or IC messengers modulate ion channels 4. Ion channels opns 5. Ions flow across membrane

Question 37

What are three methods known to terminate (inactivate/removal) of neurotransmitter?

Answer 37

1. Diffusion of the transmitter from the synaptic space 2. Cleaving the transmitter into inactive consituents through enzyme activity. (Ex: ACh is brokem down into acetate and choline by cholinesterase.) 3. Re-uptake of transmitter back into the pre-synaptoc neuron through activity of neurotransmitter transporters

Question 38

What is an example of a chemical synapse at the neuromuscular junction?

Answer 38

Voluntary neuronal stimulus (CNS) fires an action potential Motor neuron is activates and muscle dep and contracts

Question 39

What is end-plate potentials (EPPs)?

Answer 39

Depolarizations of muscle fibers caused by ACh binding to post synaptic membrane in neuromuscular junction ## Footnote neuronal ap> mediated by Na+ influx skeletal muscle endplate potential>mediated by NAChR causing Na+ coming in and K+ coming out

Question 40

____ activity depolarizes the endplate membrane

Answer 40

NAChR

Question 41

The nictotininc acetycholine receptor (nAChR) is a ____ channel receptor.

Answer 41

Ligand gated ion

Question 42

What is needed to fully activate the nAChR?

Answer 42

2 acetycholine molecules binding to a single receptor. The receptor changes conformation, opening an ion channel that is equally permeble to Na+ and K+

Question 43

Describe the molecular event of nAChR activity

Answer 43

Diffusion on Na+ and K+ across the receptor causes depolariztion, the EPP opens voltage-gated Na+ channels, which allows for firing of the APs and muscular contraction. Ions flux depends on resting Vm but NET effect is membrane dep

Question 44

nAChRs are which of the following? dimers tetramers pentamers

Answer 44

pentamers

Question 45

Summary of neuromuscular junction

Answer 45

alpha motor neuron stimulation releases ACh>activation of nAChR> depolarizing EPP> firing of skeletal muscle action potential

Question 46

What is myasthenia gravis?

Answer 46

Autoimune disease where autoantibodies targeted against nAChR on the postsynaptic membrane. Muscle weakness and fatigue result. The condition is generally treated with acetycholinesterase inhibiotrs (prevents breakdown of ACh)