Exam1Lec4Synthesis,Storage,andReleaseofNeuro Flashcards
What are gap junctions?
physical/direct connections that allow electrical coupling b/w 2 neurons
all cells have this except skeletal muscles dont have this
What are chemical synapses?
where neurotransmitters are released by the pre-synaptic cell via exocytosis
What determines whether or not a substance is a neurotransmitter?
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
What are the diff types of neurotransmitters?
small molecules, amino acids, peptides, gases,purines, biogenic amines
What is exocytosis caused by?
caused by an increase in cytosolic Ca2+ resulting from the depolarization-dependent activation of Ca2+ channels.
What is receptor activation?
Neurotransmitter binds (2 mechanism) to postsynaptic receptor, and alters (diverse response) the postsynaptic Vm
What is receptor inactivation (removal)?
Transmitters are removed from the synaptic cleft primarily through three mechanisms
What is the order of synpatic transmission?
transmitting the ap to another cell
slide 6
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
Explain electrical synapse vs chemical synpase
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.
What are pore forming proteins (connexins) connecting two cells?
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.
What are the limitations and advantages of electrical synapses?
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
What are the limitations and advantages of chemical synapses?
Limitation: slower signal transmission
Advantage: postsynpatic signal varies from presynaptic signal
as ca2+ incr, neurotrans incr
What are the 6 main types of small molecule neurotransmitters?
1) Acetylcholine
2) Amino Acids
3) Purines
4) Biogenic Amines
5) Gases (NO, CO)
6) Peptides (much larger)
- BDNF and NGF are “neurotransmitter modulators”
Amino acid transmitters can be divided into what
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
What is the most abundant neurotransmitter in the body?
Glutamate (very ubiquitos)
What are 5 examples of peptide neurotransmitters?
- Brain-gut peptides
- Opiod peptides
- Pituatary peptides
- Hypothalamic-releasing peptides
- Miscellaneous peptides
need to be injected bc digestive tract will cleave them, making them inactive
What is the life cycle of a neurotransmitter?
life cycle of neurotransmitters: 1) synthesis, 2) packaging, 3) release, 4) binding, and 5) inactivation
Explain the synthesis of catecholamines
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
What is the precursor for syntheisis of catechilamines and what is the rate limiting enzyme?
Precursor: Tyrosine (phenylalanine is the amino acid that we can get from diet)
Rate limiting: Tyrosine hydroxylase (turns tyrosine to L-dopa)
What are the primary catecholamines?
Primary catecholamines include dopamine, epinephrine, and norepinephrine
What are 2 ex of H1 antagonitsts (anti-histamines)
Diohenhydramine (lipophilic)
Loratadine/Claritin (lipophobic)
blocks histidine recp=blocks allergic rxns
Explain the synthesis of histamine
Histidine to Histamine by Histidine decarb enzyme
Explain the synthesis of serotinin
Tryptophan (essential aa found in diet) converts to 5-hydroxytryptophan then turns into 5-HT (serotonin)
Low serotonin is associated with what diseases?
Depression, OCD, ADHD
Processing of peptide neurotransmitters
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
Explain synthesis of small-molecule neurotransmitters
- Synthesis of enzymes at soma
- Transport and recycling of enzymes down axon to pre-synaptic terminal
- Synthesis and packageing of NEUROTRANSMITTERS at PRE-SYNAPTIC TERMINAL
- Release and diffusion of neurotransmitter (clear-core vesicles)
- Transport of pre-cursors into terminal
Explain synthesis of peptide neurotransmitters
- Synthesis of both neurotransmitter PRECURSORS (pro-peptide) AND ENZYMES
- Transmitter + enzymes are packages in Dense core vesicles which bud off golgi.
- Transport of enzymes and pre-peptide precursors down axon via microtubules
- Enzymes MODIFY PRE-PEPTIDES to produce ACTIVE peptide neurotransmitters at pre-synaptic terminal
- Neurotrans diffesee away
How are small molecule neurotransmitters packaged?
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.
How are larger, pro-peptide transmitters packaged?
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,
What is the membrane fusion machinery responsible for docking and priming of vesicles?
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.
V snare is associated with vesicles
SNAPs (soluble NSF attachment protein; NSF co-factors)
Fusion of vesicles to pre-synaptic membrane is Ca2+ dependent. Explain this
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
Explain how vesicle/neurotransmitter is released by excytosis?
release of a neurotransmitter
- Fusion of primed vesicles following influx of Ca2+ through activated voltage-gated Ca2+ channels.
- Synpasin formes complex of vesicles>docking> priming> snares docks vesicle to pre-synaptic membrane
- 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
Explain how a vesicle membrane can be recovered by endocytosis?
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.
what does botulism toxin do?
its neurotoixin that cleaves snares proteins and blocks exocytosis of ACh vesicles
causes paralysis of muscle
can work at different amino acid sequences of proteins
multiple targets: synpatobrevunn, syntaxin, snap-25
mechanism of postsynamotic transmitter binding
Explain ligand-gated ion channels (direct gating)
- Neurotransmitter binds (ex: GABA)
- Channel opens
- Ions flow across membrane (Cl goes into cell)
mechanism of postsynamotic transmitter binding
Explain G-protein coupled receptors (direct gating)
- Neurotransmitter binds
- G-protein is activated
- G-protein subnunits or IC messengers modulate ion channels
- Ion channels opns
- Ions flow across membrane
What are three methods known to terminate (inactivate/removal) of neurotransmitter?
- Diffusion of the transmitter from the synaptic space
- Cleaving the transmitter into inactive consituents through enzyme activity. (Ex: ACh is brokem down into acetate and choline by cholinesterase.)
- Re-uptake of transmitter back into the pre-synaptoc neuron through activity of neurotransmitter transporters
What is an example of a chemical synapse at the neuromuscular junction?
Voluntary neuronal stimulus (CNS) fires an action potential
Motor neuron is activates and muscle dep and contracts
What is end-plate potentials (EPPs)?
Depolarizations of muscle fibers caused by ACh binding to post synaptic membrane in neuromuscular junction
neuronal ap> mediated by Na+ influx
skeletal muscle endplate potential>mediated by NAChR causing Na+ coming in and K+ coming out
____ activity depolarizes the endplate membrane
NAChR
The nictotininc acetycholine receptor (nAChR) is a ____ channel receptor.
Ligand gated ion
What is needed to fully activate the nAChR?
2 acetycholine molecules binding to a single receptor. The receptor changes conformation, opening an ion channel that is equally permeble to Na+ and K+
Describe the molecular event of nAChR activity
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
nAChRs are which of the following?
dimers
tetramers
pentamers
pentamers
Summary of neuromuscular junction
alpha motor neuron stimulation releases ACh>activation of nAChR> depolarizing EPP> firing of skeletal muscle action potential
What is myasthenia gravis?
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)
