BIPN 140 Cellular Neurobiology Master Flashcards: FINAL EXAM

Define chemical synapses, outline their kinetics, direction, and give a clear example.

Synapses that alow for NT release over a synaptic cleft.

Slow kinetics.

Unidirectional.

[Description of chemical synapse in detail]

Define electrical synapses, outline their kinetic advantage, direction and give a clear example.

Synapses that facilitate direct ion transfer from neuron to neuron through the physical connection of gap junctions.

Fast kinetics.

Bidirectional.

[Description of electrical synapse in detail]

Describe ionotropic receptors. Give an example.

Receptors that have binding sites where NTs can bind and enable ion channels to open and allow ion flux. Ligand-gated ion channels.

This is a fast process.

What is the main difference in ionotropic and metabotropic receptors?

Ionotropic - physical protein conformational change to open a physical pore for ion conduction

Metabotropic - physical protein conformational change to activate a G-protein eliciting a G-protein cascade

Describe metabotropic receptors. Name three examples.

Receptors that DO NOT open themselves but undergo a G-protein specific signaling cascade that has the potential to open other ion channels as well as undergo biochemical changes in the postsynaptic cell through the activation of second messenger proteins.

This is a slow process.

These are NOT ion channels.

β-adrenergic receptors, metabotropic glutamenergic receptors, dopamenergic receptors.

Where is the G-protein bound to on the metabotropic receptor protein?

Intracellular c-terminus.

Where does the ligand bind to a metabotropic receptor protein?

Extracellular n-terminus.

What are drugs that block the function of the NTs called?

Antagonists.

What are drugs that have the same effect as NTs called?

Agonists.

What are drugs called that have the exact opposite effect of the NTs?

Reverse agonists.

What are drugs called that have a separate binding site to NTs but affect the likelihood of the NTs binding? What is this effect called?

Neuromodulators which have an allosteric effect.

What are gap junctions and where are they found? What kind of signaling mechanism do they facilitate? Describe their protein structure.

Gap junctions are clusters of intracellular channels that allow direct diffusion of ions and small molecules between adjacent cells. They facilitate electrical signaling. They are composed of hexamers with a central channel for ions. One gap junction = two hemichannels. One hemichannel = six connexons.

[Description of structure]

Define hexamer.

A group of six integral proteins called connexons per hemichannel of a gap junction.

How many connexons form one gap junction?

12

What are connexons? What molecules can diffuse through them?

Integral proteins that make up hexamers. They exist in groups of six in the gap junction. ATP, ions, second messangers.

How do ions and small molecules flow through gap junctions? In what form are they traveling?

Diffusion. Hydrated form.

What happens to extra NTs in the extracellular space of the synaptic cleft?

They are degraded by enzymes, diffuse or are absorbed by the pre-synaptic neuron/glial cells.

How can we decider whether a chemical is a NT?

They must follow the three criteria:

1. Present in pre-synaptic vesicles

2. Release upon action potential-mediated Ca+ entry

3. Bind to post-synaptic ionotropic receptors

What are some examples of small molecule transmitters that are locally synthesized in the synaptic terminal? What triggers their release?

Glutamate, GABA, ACh. They are triggered to release on a single AP with the influx of Ca++.

What are some examples of large molecule transmitters that are synthesized in the soma? What triggers their release?

Biogenic amines and neuropeptides, oxytocin, vasopressin. They are triggered to release on a many consecutive APs as one AP is not strong enough to accumulate presynaptic terminal intracellular [Ca++] which is necessary for their release.

What are clear-core synaptic vesicles? Where are they synthesized? Where are they released?

SVs that package and carry small molecule transmitters. Locally synthesizes, they are fused and reconstructed at the presynaptic terminal. They are released at the base of the synaptic terminal.

What are large dense-core synaptic vesicles? Where are they synthesized? Where are they released?

SVs that package and carry neuropeptide transmitters. They are synthesized at the soma. They are released at the neck of the synaptic terminal.

What are the function of peptidases?

They are an enzyme that eat up extra neuropeptides from the extracellular environment.

Describe volume transmission.

When neuropeptide transmitters are released diffusely in a cloud like manner and have the potential to influence targets that may be further away.

Why are neuropeptides released more rarely compared to small molecule transmitter.

Because they require consecutive action potentials in order for them to be released.

Where is ACh released? What kind of receptors do they bind to?

Neuromuscular junction. They bind to Nicotinic acetylcholine receptors nACh-Rs.

Define end-plate potential. What term is it NOT interchangeable with?

End-plate potential is the potential of the receiving muscle cell in the neuromuscular junction. Post-synaptic potential, this refers to a post-synaptic neuron NOT a receiving muscle cell.

What are the steps to chemical synaptic communication?

1. NTs are synthesized in the according vesicles.

2. AP invades presynaptic terminal.

3. Depolarization of presynaptic terminal opens VGCa++ ion channels. Influx of Ca++.

4. Ca++ influx allows for vesicle fusion in exocytosis to occur.

5. NTs are released from presynaptic to synaptic cleft to postsynaptic receptors. Excess NTs diffuse, enzymatic degradation or recycle.

6. Receptors open or close on the post-synaptic cell.

7. Postsynaptic current causes EPSP or IPSP.

8. Clear core synaptic vesicles are constructed and refilled with NTs.

Define miniature end-plate potentials.

Miniature end-plate potentials caused by random vesicle fusion at the presynaptic terminal. This event is random and spontaneous.

Describe Katz's Quantal Nature of Neurotransmission.

The idea that neurotransmitter release is in discrete quanta. NTs are packaged in SVs. EEPs are built on MEEPs. Random SV fusion causes MEPPs. There are the same number of neurotransmitters per SV. Each stimulus is a quanta. Neurotransmission is driven by quantal events.

What are the steps in the lifecycle of a synaptic vesicle? How long does it take?

1. Endosome will engage in budding of the endosome.

2. Beginning stages of exocytosis will occur here. Beginning with docking, priming then fusion.

3. Beginning stages of endocytosis begin here. Starting with budding from the synaptic terminal membrane and endosome fusion.

About one minute.

What is the endosome?

An intracellular organelle that facilitate synaptic vesicle recycling.

What are the two mechanisms involved in synaptic vesicle construction and fusion? Which process has slow and fast kinetics?

Endocytosis (slow) and exocytosis (fast), respectively.

What is the function, budding?

Budding is the process of pinching off new synaptic vesicles from either the endosome or the synaptic terminal membrane.

Describe the specific steps in exocytosis and endocytosis respectively.

We start with the reserve pool of SV in the presynaptic terminal...

EXO:

1. Synapsins and CaMKII mobilize SV to prepare for docking.

2. GTP-binding SNARE proteins allow for the SVs to dock to the base of the synaptic terminal.

3. Priming process begins where synaptotagmin bind to SNARE proteins. This prepares the SV for Ca++ mediated exocytosis.

4. Fusion occurs where Ca++ influx allows for Ca++ bind to synaptogamin and initiate the fusion process and NTs are released into the synaptic cleft.

ENDO:

6. After exocytosis concludes, the process of coating begins where Clathrine molecules shape the synaptic vesicles acting as a cytoskeleton as NTs are collected in the SV then budded into the cytoplasm.

7. Post-budding, Clathrine unhinge their cage-like structures from the newly formed SV (uncoated from) and merge with the endosome concluding endocytosis.

What is the synapsin protein and its function? What triggers it's function?

A protein that holds newly made SVs together in the reserve pool. Synapsin releases SV upon phosphorylation.

What are SNARE proteins? Describe where the proteins originate.

SNARE proteins are a complex of proteins that bind together. This is a complex of synaptogamin, synaptobrevin, syntaxin and SNAP-25.

SV: synaptogamin protein pair superior to synaptobrevin protein pair. Bilateral articulation to the SV.

Synaptic terminal membrane: syntaxin is the lateral protein pair, SNAP-25 is the medial protein pair. Dual pair articulation on the synaptic terminal membrane.

What triggers fusion of SVs to the presynaptic membrane.

Ca++ influx through Ca++ ion channels that live at the base of the synaptic terminal.

What protein pinches off the newly made synaptic vesicles int heir caged Clathrine form?

Dynamin.

What is the role of actin in the process of endocytosis?

Actin projections inside of the cell launches newly caged SVs away from the cellular membrane.

Where does in coming Ca++ bind to during exocytosis?

Synaptogamin.

Describe the specific steps to exocytosis in regards to the SNARE protein complex fusion process.

1. SV approaches the synaptic terminal membrane. All proteins are free of fusion.

2. Syntax, SNAP-25 and Synaptobrevin begin to from the SNARE complex.

3. Synaptogamin bind to the three proteins completing the SNARE complex.

4. Ca++ enters the cell through ion channels that live on the synaptic terminal membrane. Ca++ binds to synaptogamin initiating the fusion process of the SV and the cellular membrane.

What are excitatory and inhibitory responses dependent on?

Neurotransmitters.

What is a trick to remember what channels are ionotropic?

Ionotropic - ion channel

What is a trick to remembering what channels are metabotropic?

Metabotropic: meta = prefix that means beyond, extraordinary. G-protein cascades are beyond complicate and extraordinarily complex.

Why are nACh-Rs named nicotinic?

Because ACh-Rs can also interact with nicotine.

What are characteristics of ACh-Rs in the neuron?

Non-selective cation channel, causes depolarization.

What is the heterotrimeric G-protein bound to metabotropic receptors? How do they split off and where do they bind postsynaptic intracellularly?

α-subunits, β-subunits, γ-subunits. α- subunit (binds to effector proteins) and β-subunit/γ-subunit complex (modulate ion channels and bind back to the metabotropic receptor).

Where do resting membrane potentials reside in muscles?

Slightly more negative than neurons.

What is the reversal potential of n-AChRs?

0mV

How can we measure the reversal potential of a receptor?

By finding the value of the end-plate current by utilizing the conductance of the NT, membrane potential and equilibrium potential.

Imagine a graph that plots the Ohmic relationships of equilibrium potentials of K+, Na+ and Cl-. Reading from left to right what order are the E(ion)'s in? What direction do they fall in? What ions are associated with a n-AChR, where is it's reversal potential and the involved ion reversal potentials?

How can we manipulate the n-AChRs in the following scenarios?

1. Moving the Ohmic trend line to the left.

2. Moving the Ohmic trend line to the right.

E(K+), E(Cl-), E(Na+) bottom left corner to right top corner.

n-AChRs bottom left corner to top right corner E(rev) = 0, E(K) most left, between E(K) and E(rev) lives E(Cl), most right lives E(Na)

1. Decreasing extracellular [Na+] moves the trend line to the left because very positive E(Na+) 70mV will move closer to the value E(rev) 0mV shifting the trend line to the left. (Think: less dramatic [Na+] gradient will equalize with less Na+ ion flux at a quicker rate easily)

2. Increasing extracellular [Na+] moves the trend line to the right because very positive E(Na+) 70mV will move further away from the value E(rev) 0mV shifting the trend line to the right. (Think: a more dramatic [Na+] gradient will only equalize with more Na+ ion flux slowing the rate of equalization and the more dramatic gradient makes this task slightly more difficult)

What determines relative contribution of any permeable ion?

Driving force.

What are the effects on the cell of excitatory and inhibitory synapses? How does this affect equilibrium potential distances?

Excitatory synapses cause depolarization and make it easy for the cell to elicit an AP. Decrease distance between E(ion) and E(rev).

Inhibitory synapses cause hyperpolarization making it harder for the cell to elicit an AP. Increases distance between E(ion) and E(rev).

Define shunting inhibition.

A term describing the effect in which even if you open an ion channel that cannot flux ions, it still decreases resistance of the membrane inviting leakage of current.

Describe characteristics of excitatory and inhibitory neurons as well as what species of ions they flux.

Excitatory flux cations and neuronal axons are long.

Inhibitory flux anions and neuronal axons are short.

In what manner do ion channels function?

All-or-none fashion.

Where are excitatory synapses inputted?

Dendrites and synaptic terminal bulbs.

Where are inhibitory synapses inputted?

Anywhere on the cell!

What neurotransmitters are excitatory?

Glutamate, ACh, Epi/NorEpi

What neurotransmitters are inhibitory?

GABA, Glycine

Describe what an IPSP as well as an EPSP current would look like on a graph over time (x-axis).

IPSP - small inward current

EPSP - tall peaking outward current past threshold

Describe what an IPSP and EPSP current would look like on a graph along time (x-axis).

These two forces will "cancel" each other out and form a small outward current.

How can we determine by a current vs time graph if we have an IPSP or EPSP?

If E(rev) then is above threshold then it is an EPSP. If E(rev) is below threshold then it is an IPSP.

Will a single synapse drive an action potential?

No. One synapse will influence modest membrane change.

How do neurons integrate inputs?

In space and time.

Describe the following relationship: length and degradation of current and how it affects the neuron.

Longer space/length will cause degradation of a current and smaller affect on the neuron.

Shorter space/length will allow for lesser degradation and greater affect on the neuron.

Describe the following relationship: time and stimulus and how it affects summation.

Lengthier time in between stimuli will not allow summation.

Shorter time in between stimuli will allow for summation.

What do the final affect of somatic voltages depend on?

Distance and timing of synaptic input.

Define spatial integration.

When two stimuli elicited at two different locations on the neuron of the same excitatory or inhibitory effect and converge when they meet at the axon. This produces an EPSP that has a large and steep peak. The resulting integrated EPSP is greater than any single EPSP due to summation. Because of Summation, the traveling EPSP subjected to very little current degradation.

Define temporal integration.

Is when integration of two of the same inputs to the same location produce a compounded EPSP. This compounded EPSP doesn't have a large peak therefore the traveling compounded EPSP is subject to current degradation.

What kind of property do dendrites have that amplify dendritic input?

Active ionic properties. This is driven by Ca++ ion channels that produce active conductances to amplify dendritic input.

Describe the mechanism of backward-propagation.

Backward-propagating action potentials travel backward up the dendrite. This voltage change opens Ca++ ion channels in the dendrites and compound with the initial input. Once the currents compound then they move in an anterograde fashion. This compounded current causes a large positive voltage increase strictly driven by Ca++ which sequentially produces sudden burst of action potentials in a row. The product of this mechanism is fast depolarization of the neuron. The burst of action potentials depolarize the neuron through amplification of what may have initially been a weak stimulus.

How is ACh usually released?

From CNS to PNS.

How is ACh synthesis catalyzed?

Through cholinacetyltransferase ChAT.

What is the function of VAChT?

VAChT loads SV with ACh.

What does the drug curare cause?

Paralysis through disruption of n-AChRs.

Describe the molecular structure of n-AChRs. Where does ACh build?

Pentamers (five-subunits), each subunit has a cellular domain and four transmembrane domains. ACh binds to the α-subunit extracellularly.

Describe the molecular structure of m-AChRs.

Seven-transmembranal receptors like all GCPRs.

What is the primary exitatory neurotransmitter in the CNS? What is it synthesized from and by what molecule?

Glutamate. Synthesized from glutamine by gluaminase.

What are the receptors to glutamate? Describe their differences.

AMPA: tetramer GluA1-4, all subunits bind to glutamate, conducts Na+/K+, fast inward current, reversal potential 0pA

NMDA: tetramer with two GluN1 subunits and two GluN2 subunits, conducts Ca++/Na+/K+, prolonged inward current, reversal potential 0pA

What is the postsynaptic response to glutamate in AMPA-Rs?

Conduction of ions occur at rest upon glutamate binding.

What is the postsynaptic response to glutamate in NMDA-Rs? What are these receptors most permeable to?

Conduction of cations when the neuron is significantly depolarized. Ca++.

Describe the relationship between NMDA-Rs and Mg++ ions.

Mg++ ions are attracted to NMDA-Rs because the interior canal is negatively charged at rest. It clogs this receptor at rest and unclogs when AMPA-Rs depolarize the cell allowing ion flux in NMDA-Rs.

What is the primary inhibitory neurotransmitter in the CNS? What molecule is it derived from and by what enzyme?

GABA. Glutamate acid decarboxylase or GAD which synthesizes glutamate into GABA.

What is the general steps to GABA synthesis?

Glucose -> Glutmate -> GABA

Glutamate and GAD make GABA.

What is VIAAT?

Vesicular inhibitory amino acid transporter. It loads GABA into SVs.

What is GAT?

A GABA transporter channels in neurons and glia cells that remove excess NTs from the synaptic cleft through the process of reputable.

What ions do GABA(A)-Rs conduct? What effect does the ion have on the neuron? What are the characteristics of these receptors?

Cl- anions. Cl- hyperpolarizes the neuron and inhibits it from firing APs.

* Inside their pore is positively charged attracting Cl-

* Pentameter

* Two α-subunits

* Two β-subunits

* One γ-subunit

* Multiple binding sites

Hyperpolarization has what affect on action potentials?

Makes it harder for the cell to fire APs.

Depolarization has what affect on action potentials?

Makes it easier for the cell to fire APs.

What type of receptors are GABA(A)-Rs and GABA(B)-Rs?

Ionotropic and metabotropic respectively.

What ions do GABA(B)-Rs conduct? What effect does the ion have on the neuron? What are the characteristics of these receptors?

K+ (activates) and Ca++ (ibhibits) cations. Depolarizes the neuron to make it easier to fire APs.

* Heterodimer B1 and B2 subunits

* Extracellular domain that changes shape upon ligand binding

What are the three catecholamines?

Dopamine, norepinephrine, epinephrine.

How are catecholamines synthesized? Where are they found?

1. Tyrosine

2. DOPA

3. Dopamine

4. Norepinephrine

5. Epinephrine (catecholamines are found in CNS and PNS)

What are catecholamines? What types of receptors do they have?

Neurotransmitters that have a variety of function throughout the nervous system. GCPRs.

What dopamine receptor domains are excitatory and inhibitory? What kind of receptor is this?

D1 and D5 excitatory. D2, D3, D4 inhibitory. GCPR. Reside in CNS.

What epinephrine/norepinephrine receptor domains are excitatory and inhibitory? What kind of receptor is this?

α1 excitatory and α2 inhibitory. GCPR. Reside in CNS and PNS.

What are the stages in neuropeptide synthesis?

1. Pre-propeptide

2. Propeptide

3. Active peptide

4. Active peptides (plural!)

What are the stages in signaling cellular response?

Signaling Cell -> Signal -> Receptor -> Effector Molecule -> Response