Cellular Neuroscience
Name an excitatory ionotropic receptor
- AMPA receptor - nicotinic Acetylcholine receptor - NMDA receptor
Name an inhibitory ionotropic receptor
- GABA-A receptor - GABA-C receptor - Glycine receptor
Name the 2 functional classes of calcium channels and a representative in each class (use either the gene name classification or the "...[blank]-type channel" classification)
- High-threshold channels (HVA) Cav1.x (L-type channels), Cav2.1 (P/Q-type channels), and Cav2.2 (N-type channels) - Low-threshold channels (LVA) Cav3.x (T-type channels)
Name two of the functions of astrocytes in the nervous system
- Support endothelial cells that make up the blood-brain barrier - Regulate the concentration of ions in the extracellular space at synapses - Transmitter uptake and release (recycling) - Contribute to pH homeostasis in the brain - Waste recycling - Regulation of the antioxidant glutathione
Based on the results of their voltage-clamp experiments Hodgkin and Huxley were able to make the following prediction(s) about the ion channels that underlie the action potential:
- The Na+ channels must inactivate, because the current goes off even when it is depolarized. - The K+ channels do not inactive - if the cell is depolarized, they are open - The activation (open probability) of both channels is voltage-dependent All of the above are true
How fast an action-potential propagates down the axon depends on
- both passive current spread and active current flow through voltage dependent sodium channels - the resistance of the membrane - whether the axon is myelinated or not - the length constant (lambda)
What are one or two things that are noteworthy about the NMDA receptor?
- permeable to calcium - normally blocked by magnesium - requires glycine as co-facto
You record from a squid giant axon in which the reversal potential for potassium ions is at -90 mV. You hyperpolarize the membrane to -110 mV. What will happen?
- potassium ions will flow against their concentration gradient into the cell - an inward current can be measured
Listed below are the events that make up chemical synaptic transmission. 1. Diffusion of transmitter across the synaptic cleft 2. Depolarization of the presynaptic terminal 3. Vesicle fusion with plasma membrane 4. Opening of voltage-gated ion channels 5. Activation of presynaptic, calcium-sensitive proteins Which of the following is the correct sequence of these events?
2; 4; 5; 3; 1
What type of protein is the Ras protein?
A (small) G-protein / small GTPase
Capacitance is...
A measure of the membrane's ability to hold an electrical charge.
How would you describe the currents in the image, and what is the name of the gene in drosophila (fruit flies) that encodes the channels that are responsible for this type of current? [Test 2, Figure 2]
A-type potassium current (fast inactivating). The channel proteins are produced by the Shaker gene
Activation of a G-alpha subunit of G-proteins can lead to (directly or indirectly)
A. Activation of adenylate cyclase B. cAMP formation C. PKC activation (D. All of the above)
Activation of Phospholipase C (PLC)
A. Cleaves PIP2 into IP3. B. Cleaves PIP2 into DAG C. Leads to release of calcium from intracellular stores D. Leads to activation of protein kinase C (E. All of the above)
Protein phosphatases are
A. Enzymes B. Responsible for dephosphorylation of phosphate groups from proteins (F. A&B are correct)
Phosphorylation
A. Occurs often at serine and threonine residues C. Involves ATP (E. A&C are correct)
The transcription factor CREB can be activated by
A. Protein kinase A (PKA) B. Mitogen-activated protein kinase (MAPK) C. Calcium D. CaMK-IV (a variant of CaMK-II) (E. All of the above)
Enkephalins
A. Regulate pain perception B. Are released from the periaqueductal gray C. Are released from interneurons in the spinal cord (D. All of the above are true)
Gap junctions
A. allow for electrical coupling between cells B. are a means to establish and spread network oscillations C. exist between glia cells D. are established by specialized proteins called connexins (E. all of the above)
The nicotinic Acetylcholine receptor
A. is a non-selective cation channel C. evokes EPSPs, because at the resting membrane potential the driving force for Na+ is higher than that for K+ (E. A&C are correct)
Synaptic inhibition can occur through
A. opening of potassium channels B. opening of chloride channels C. both metabotropic receptors and ligand-gated channels D. increases in conductance without changes in membrane potential (E. all of the above)
The role of SNARE proteins is to
A. tether vesicles to the reserve pool B. to form coated pits during endocytosis C. establish "bridges" between the presynaptic and postsynaptic side of a synapse during development D. transport vesicles from the reserve pool to the active zone (mobilization) (E. none of the above)
Mitochondria are considered the cell's power plants because they generate energy in the form of:
Adenosine tri-phosphate (ATP)
In voltage-clamp experiments an action potential is characterized by
An early inward current that depends on sodium ions, followed by a delayed outward current that depends on the flow of potassium ions
Protein kinases
Are normally autoinhibited by their regulatory subunit(s). Binding of a second messenger releases the catalytic subunit, allowing it to phosphorylate target proteins
Structure _______ is the main structure that receives incoming signals from the axons of other cells. [Test 1, Figure 2]
B
This current-voltage plot (I-V curve) shows the currents that occur during an action potential. Use the marked points to answer the following question: Which point indicates the reversal potential for potassium? [Test 1, Figure 1]
B
The sodium-potassium pump
B. requires energy in the form of ATP to do its work D. transports ions against their concentration gradient (E. B & D are correct)
Mitogen-Activated Protein Kinase (MAPK) is a protein kinase that
B. Is activated by other kinases C. Regulates gene transcription through activation of CREB (D. B&C are correct)
Which of the following is true about the molecular structure of voltage-gated sodium channels?
B. The α subunits are single polypeptide chains organized in four homologous domains, which each contain six transmembrane alpha helices (S1-S6) and an additional pore loop located between the S5 and S6 segments D. The pore-forming α subunit is accompanied by 1 or 2 β-subunits which modulate channel gating and localization of the channel in the membrane. (F. B&D are true)
During an action potential the membrane potential moves towards the reversal potential for sodium ions (ENa) but does not quite reach ENa. This is because:
Because at the resting membrane potential the membrane is also somewhat permeable to other ions like sodium. The influx of sodium slightly depolarizes the membrane potential above the equilibrium potential of potassium.
Why is the resting potential not identical to the equilibrium potential of potassium?
Because at the resting membrane potential the membrane is also somewhat permeable to other ions like sodium. The influx of sodium slightly depolarizes the membrane potential above the equilibrium potential of potassium.
Heuser and Reed showed that if you block voltage-gated K+ channels with 4-AP you will get more transmitter release at the presynaptic terminal. This is because....
Blocking voltage-gated K+ channels with 4-AP will reduce or prevent the repolarization of the action potential. The broader AP will lead to more/longer depolarization at the presynaptic terminal. This in turn will activate more voltage-gated calcium channels in the presynaptic terminal, leading to more calcium influx. More calcium influx equals more transmitter release.
How can potassium (K+) channels select potassium ions over sodium (Na+) ions?
Both Na+ and K+ ions must shed their hydration shell when passing through the channel. At the site of the selectivity filter within the pore the walls are too far apart to stabilize a dehydrated Na+ ion
This current-voltage plot (I-V curve) shows the currents that occur during an action potential. Use the marked points to answer the following question: Which point on the graph provides the best evidence for the time-dependent inactivation of the sodium channels? [Test 1, Figure 1]
C
Name one of the proteins that is needed to help RNA polymerase assemble on the DNA promoter region before transcription can begin
CREB; transcription factor(s); co-activator complex
Adenylate cyclase
Catalyzes the conversion of ATP to cAMP
Describe the state of the voltage-gated channels in the membrane of a typical neuron just after the action potential has reached its peak.
Channels that underlie fast voltage-gated sodium currents are inactivated and voltage-gated potassium channels that contribute to the delayed rectifier potassium current are activated.
Name the two main proteins involved in endocytosis and describe their roles in the process.
Clathrin triskelia, form coated pits. Dynamin, pinches of coated vesicle
A scientist wishes to develop a new drug that prevents synaptic communication via neuropeptides but not small molecule neurotransmitters. Which mechanism would be a good target for his drug?
Disruption of fast axonal transport
In the process of testing a new environmental pollutant as a potential neurotoxin you discover that the levels of tyrosine hydroxylase (TH) are reduced in the brain. Based on these data, which of the following neuronal cells would you predict are affected by this neurotoxin?
Dopaminergic and noradrenergic.
Which of the following statements about protein kinase-based signaling is FALSE?
Each protein kinase has just one specific target protein that it phosphorylates
Name a substance that acts as a retrograde neurotransmitter
Endocannabinoids (Anandemide, 2-AG), or Nitric Oxide (NO)
Name one of the 3 opioid peptides
Endorphins, Enkephalins, Dynorphins
The release of neurotransmitters into the synaptic cleft is called
Exocytosis
Pick the correct sequence from G-protein to effector molecule
G-alpha s (stimulatory) - Adenylate cyclase - cAMP - PKA
The presence of which of the following compounds or proteins in a cell makes it quite likely that the cell is a GABAergic neuron?
Glutamic acid decarboxylase (GAD)
Which of the following is NOT a catecholamine?
Histamine
You are recording from a cell in which the membrane potential (Vm) is at -72 mV. Based on your calculations, the equilibrium potential of potassium (EK) is -84 mV for this cell. How could you make K+ move into the cell?
Hyperpolarize Vm to -102 mV
Under certain conditions release of GABA can lead to depolarization of the postsynaptic cell. This occurs
If the chloride (Cl-) reversal potential is more positive than the resting membrane potential
Which of the following statements about the channels that generate transient A-type potassium currents is NOT true?
In mammals they are represented by Kv2.1 and Kv2.2 channels, which closely resemble the drosophila channels encoded by the Shaw gene.
The refractory period(s) following an action potential is the result of which 2 factors/mechanisms (what currents/channels are involved)?
Inactivation of voltage-gated sodium channels and continued activation of delayed-rectifier potassium channels
How would application of a Ca2+ channel blocker affect the function of a synapse?
It would eliminate the postsynaptic potential and the presynaptic Ca2+ current.
What is the function of kinesin?
Kinesin is a motor protein that moves organelles along microtubular tracks towards the "+" end of the microtuble (towards the periphery, away from the soma)
What is the role of microglia in the nervous system?
Microglia destroy pathogens and remove dead neurons. Microglia work with astrocytes to repair or isolate lesions in the nervous system. Microglia release inflammatory cytokines, as well as neurotrophic factors.
Which of the following is NOT true? Transcription factors
Need to be dephosphorylated to have an effect
Which of the following is NOT true about postsynaptic receptors?
Once synapses have formed the same receptors remain in the postsynaptic density to enable stable memories
The _______ of a voltage-gated calcium channel is responsible for the ion selectivity of the channel.
P region (pore loop)
What is (poly-)ubiquination and what is it used for?
Proteins are tagged for degradation with a small protein called ubiquitin. This results in a polyubiquitin chain that gets bound to the proteasome, allowing it to degrade the tagged protein.
IP3 and DAG are examples of
Second messengers
Which of the following is NOT a characteristic of the classical (NMDAR-dependent) long-term potentiation (LTP)?
Small elevations in postsynaptic calcium levels lead to activation of protein kinase A (PKA).
What is the name of the protein that tethers vesicles in the reserve pool ?
Synapsin
What is the name of the calcium sensor that sits on the synaptic vesicle?
Synaptotagmin
What would you use the Nernst-equation for?
The Nernst equation is used to calculate the equilibrium (reversal) potential for a single type of ion.
What will happen if you greatly decrease the concentration of sodium on the outside of the cell?
The amplitude of the action potential will decrease.
Which evidence supports the assertion that the macroscopic Na+ current is the sum of many microscopic Na+ currents?
The averaged collective response of single channels resembles the time course of the macroscopic current.
What is the cell membrane made up of?
The cell membrane is a phospholipid bilayer in which transmembrane proteins "float"
The activation and effects of Protein Kinase C (PKC) depend on
The cleavage of PIP2 into IP3 and DAG. Binding of DAG then enables PKC to phosphorylate target proteins in the membrane
Which of the following statements is best illustrated by this graph? [Test 2, Figure 3]
The gating of Na+ channels is voltage dependent.
The activity of RGS proteins (sometimes also called GAPs) leads to
The hydrolysis of GTP to GDP, which stops the activity of the G-alpha subunit
In the communication between neurons, how is the intensity of a signal encoded?
The intensity of a signal is coded via the frequency of action potential firing.
You are recording the resting membrane potential of a squid giant axon. What will happen to the resting potential if you add potassium chloride to the external medium?
The membrane potential would become depolarized
The nucleus of the cell contains
The nucleolus and chromosomes
Define the threshold of an action potential in terms of currents
The threshold of the action potential is the reached when the inward current through voltage-gated sodium channels outweighs the outward current through voltage-gated potassium channels and leak K+ channels.
In Figure B you see recordings of isolated sodium currents (evoked by the voltage-step protocol shown in A). Label the 2 components of the current indicated at the white and black arrow, respectively (what do you measure there?) [Test 2, Figure 1]
The white arrow indicates the transient, inactivating sodium current. The black arrow indicates the persistent, non-inactivating component of the sodium current (INaP).
If the membrane is voltage-clamped at the reversal potential of a given ion, which of the following statements is TRUE?
There is no net movement of these ions across the membrane
All of the following is true about protein kinases, EXCEPT
They have a regulatory subunit that binds to protein phosphatases
Parkinson's disease is a movement disorder that is due to
a loss of neurons in the midbrain that produce dopamine
The proteins that establish and maintain ion gradients are called
active transporters
When a muscle fiber is held at a voltage of 0 mV at the neuromuscular end plate, acetylcholine no longer produces a current because
an inward current via sodium is balanced by an equally strong outward current via potassium.
Cocaine leads to a euphoric "high". The cellular mechanism of this high results from cocaine ....
blocking dopamine reuptake (via DAT)
Neurons can fire different patterns of action potentials. One example of this is the so-called "burst" firing. Burst-firing is strongly dependent on dendritic:
calcium channels
If you were to microinject calcium into the presynaptic terminal you will
get transmitter release in the absence of action potentials
The "active zone" in the presynaptic terminal of the neuro-muscular junction is characterized by a
high density of voltage-gated calcium channels
The transmitter GABA excites immature cortical neurons because
immature GABA-receptive neurons express a large number of Na+/K+/Cl- co-transporters
Insecticides and the nerve gas sarin
irreversibly block acetylcholine-esterase (AChE), leading to overstimulation of postsynaptic target cells.
The Goldman equation is suited to calculate the resting membrane potential because...
it takes the contribution of several ions and their relative permeability into account.
The myelin-sheath of oligodendrocytes speeds up action potential propagation along the axon by...
none of the above.
According to the SNARE hypothesis, the V-SNARE protein ___________ needs to interact with __________ (T-SNARE protein) to pull the vesicle and cell membrane together.
synaptobrevin, SNAP25
All small molecule transmitters (classical neurotransmitters) are
synthesized in the synaptic terminal
Cells receive and integrate many synaptic inputs. Eventually, an action potential may be initiated from the sum of these potentials. The site of the initiation of the action potential is:
the axon hillock below the soma
Exocytosis of neurotransmitter (quantal release) requires the following step to occur:
the interaction of synaptotagmin and neurexin
The spatial summation of two, graded postsynaptic potentials at the dendrite of a neuron is influenced by which of the following?
the length constant lambda
If a cell has a large length constant this means that...
the likelihood that two distant synapses may interact to influence the action potential generation at the soma is increased.
Which part of a voltage-gated potassium channel is responsible for "sensing" changes in the membrane potential?
the positively-charged amino acids on the S4 segment
MEPPs are an indicator for vesicular (quantal) release at chemical synapses because
they are a fraction of EPPs
All of the following is true for the currents flowing through individual voltage-gated potassium (K+) channels, EXCEPT:
they are blocked by calcium chelators (e.g. BAPTA )
Ribosomes read the information in the RNA and use it to create proteins. This process is known as:
translation
AMPA receptors
typically show low calcium-permeability due to an arginine residue on the GluA2 subunit that repels calcium
Ion exchangers
use the chemical energy stored in the concentration gradient of one type of ion to move another type of ion against its concentration gradient
