Neurons and Glia 1 Flashcards
Give the ‘official’ definition of ‘reversal potential’. (1)
The potential difference across a membrane when there is no net movement of ions.
Give another name for reversal potential. (1)
Equilibrium potential
Which ions (out of K, Na, Cl, and Ca) are predominantly extracellular? (1)
Na
Cl
Ca
Which ions (out of K, Na, Cl, and Ca) are predominantly intracellular? (1)
K
Describe what is meant by the term ‘electrochemical gradient’. (1)
A combination of the concentration (diffusion) gradient of an ion and the electrical gradient acting across the membrane.
What is the function of the Nernst equation (what does it calculate)? (1)
The reversal potential of an ion.
Give the ‘pure’ form of the Nernst equation. (1)
Ex = RT/zF ln (xo)/(xi)
Give the simplified form of the Nernst equation for a mammal at 37 degrees. (1)
Ex = 61.5 log (xo)/(xi)
How do you convert from ln to log10? (1)
Multiply by 2.303
What does R stand for in the Nernst equation? (1)
Gas constant
What does z stand for in the Nernst equation? (1)
Ion valence
What does F stand for in the Nernst equation? (1)
Faraday constant
What does T stand for in the Nernst equation? (1)
Temperature (Kelvins)
According to the Nernst equation, what would Ex of an ion be if the intracellular and extracellular concentrations were equal? (1)
0mV
According to the Nernst equation (for a positively charged ion), if the extracellular concentration is higher than the intracellular concentration, will Ex be positive or negative? (1)
Positive
According to the Nernst equation (for a positively charged ion), if the extracellular concentration is lower than the intracellular concentration, will Ex be positive or negative? (1)
Negative
What is log10 (1)? (1)
0
Why are astrocytes important when looking at the Nernst equation? (2)
Astrocytes are permeable to K only
so Em will be equal to Ek.
When converting the Nernst equation for Ek to an equation for a straight line, we can disregard [K]i. Why? (2)
Because it takes very few ions to move to carry charge across the membrane.
Therefore, a change in voltage will only result in a negligible change in intracellular ion concentration.
How does increasing the extracellular potassium concentration affect the value of Ek and why? (4)
As [K]o increases, Ek increases.
Because the concentration gradient across the membrane is decreased,
and a smaller electrical gradient is required to oppose the concentration gradient,
and stop the net movement of ions across the membrane.
What would be the clinical consequence of a rise in extracellular potassium? (2)
Membrane becomes depolarised because Ek increases,
and the neurone then fires too easily.
Describe how an astrocyte is able to detect neuronal activity away from the synapse. (3)
During the AP there is efflux of potassium into the extracellular space.
This affects Vm of the astrocyte (makes it less negative)
The astrocyte becomes depolarised.
Give a brief description of how potassium activity in astrocytes can quantify neuronal activity. (3)
APs release potassium into extracellular space which changes Vm of astrocytes.
Using the change in Vm, we can use the Nernst equation
to work out the change in [K]o which occurs with an action potential.
Describe a method to work out [K]i of astrocytes using electrodes. (4)
Vm of astrocyte is equal to Ek.
When [K]i = [K]o, Ek and Vm are zero.
Keep bathing astrocytes in known concentrations of [K]o until Vm=0.
When Vm=0, [K]i will be the same as [K]o.
Why can’t the Nernst equation be used to calculate Em of neurones? (1)
Neurones are permeable to more than one ion.
Describe how the Nernst equation predicts the direction and speed with which a particular ion will move across a membrane. (2)
Ion moves across the membrane in the direction that will cause Em to move towards Ex.
The greater the difference between Em and Ex, the quicker/more ions will move.
True or false? (1)
An ion will always move down its concentration gradient, even if it means Em will move away from Ex.
False - an ion will always move so that Vm moves towards Ex, even if that means moving against its concentration gradient.
Calculate log10 (0.01). (1)
-2
Calculate log10 (0.1). (1)
-1
Calculate log10 (10). (1)
1
Calculate log10 (100). (1)
2
How does increasing [K]o affect the peak of the action potential? (1)
It doesn’t - the peak is due to sodium only
Why does the afterhyperpolarisation get smaller as [k]o increases? (2)
As [k]o increases there is less of a concentration gradient so Ek gets closer to zero.
Because Vm will approach Ek during repolarisation, it will not go as negative if Ek is not as negative.
Describe what is meant by local currents, in relation to the axon. (1)
Excitation in a region of axon will send small currents down the axon and out through the membrane.
Give three effects on the action potential of decreasing [Na]o. (3)
- The conduction velocity decreases
- Rate of upstroke decreases
- Action potential amplitude decreases
Describe the passive phase of the action potential rise. (3)
- Local currents depolarise small sections of membrane
- Up to the threshold value only
- Vm rises slowly
Describe the active phase of the action potential rise. (3)
- Threshold is reached and Na channels open
- The membrane has a rapid-onset, transient, increased conductance to Na
- Vm rises rapidly
How does a membrane’s permeability to different ions affect its Vm? (1)
At any instant, the membrane potential will approach the equilibrium potential of the ion to which it is most permeable at that instant.
Describe the magnitude and direction of the electrochemical gradient acting on Na at rest. (2)
Large gradient
driving Na into cell.
Describe the magnitude and direction of the electrochemical gradient acting on K at rest. (2)
Small gradient
driving K out of cell.
At rest, why isn’t Em halfway between ENa and Ek?
Where does it rest? (2)
Because the membrane is much more permeable to K than Na.
Em lies closer to Ek.
If the electrochemical gradient acting on Na is larger than the one acting on K at rest, why doesn’t more Na move into the cell? (1)
Na channels are not open
True or false? (1)
The voltage-gated opening of sodium channels during the rising phase of the action potential is an example of negative feedback.
False - it is an example of positive feedback
What accounts for the increased conductance to K during the repolarisation phase of the action potential? (1)
Delayed opening of voltage-gated K channels
True or false? (1)
When depolarisation occurs, sodium channel inactivation gates are triggered to close.
True - however activation gates open more rapidly to allow transient Na influx, and inactivation gate closing is delayed.
Describe the role of the Na channel inactivation gate in the neuronal refractory period. (3)
After depolarisation there is delayed closing of the inactivation gate.
The inactivation gate remains closed until the cell becomes repolarised.
Only then can another AP be stimulated to occur.
Describe the states of the activation and inactivation gates of the sodium channel during the rising phase of the action potential. (2)
Activation gates open
Inactivation gates open
Describe the states of the activation and inactivation gates of the sodium channel during the resting phase of the action potential. (2)
Activation gate closed
Inactivation gate open
Which equation would be used to work out Em of a cell which is permeable to more than one ion? (1)
Goldman Hodgkin Katz
What is the Goldman Hodgkin Katz equation? (1)
Em = RT/zF ln (PNa[Na]o + Pk[k]o)/(PNa[Na]i + Pk[k]i
What is the effect of increasing PNa on Vm?
Consider how this changes if [k]o were to be increased. (2)
Increasing PNa increases Vm.
As [K]o increases, this effect diminishes
because as [k]o increases it begins to dominate the GHK equation.
At low [k]o, which ion dominates the GHK equation? (1)
Sodium
How are PNa and Pk expressed in the GHK equation? (2)
Pk = 1
PNa expressed relative to Pk.
True or false? (1)
The numerator of the GHK equation can be treated as a constant.
False - the denominator (PNa[Na]i + Pk[k]i) can be treated as a constant.
Describe the effect (and the magnitude of the effect) of [k]o on the resting phase of the action potential. (2)
Low [k]o makes Vm slightly more negative.
Small effect because membrane is also slightly permeable to Na.
Describe the effect (and the magnitude of the effect) of [k]o on the peak of the action potential. (2)
No effect
The membrane is almost exclusively permeable to Na.
Describe the effect (and the magnitude of the effect) of [k]o on the afterhyperpolarisation phase of the action potential. (2)
Lower [k]o produces larger (more negative) hyperpolarisation.
Large effect because membrane is almost exclusively permeable to K.
At high concentrations of Na, what effect size will decreasing [Na]o have on ENa? (1)
Very little decrease
At low concentrations of Na, what effect size will decreasing [Na]o have on ENa? (1)
Large decrease
According to the GHK equation, why does changing [Na]o at resting membrane potential have very little overall effect on Em? (1)
PNa is very small
Complete the sentence. (1)
At low [K]o, the ………………… ion contributes more to the position of Vm.
Sodium
Complete the sentence. (1)
At high [K]o, the ………………… ion contributes more to the position of Vm.
Potassium
How does the neuronal Vm compare to the astrocyte Vm at the same [k]o? (1)
Less negative
If 10mM K was added to the extracellular fluid in the brain, would Vm of the neurone or the astrocyte increase more? (1)
Astrocyte
In an experiment where [k]o is gradually increased and change in neurone and astrocyte Vm is compared, would a bigger difference be seen at low [k]o or high [k]o? (1)
Low
Give two differences between myelin in the CNS and myelin in the PNS. (2)
- CNS provided by oligodendrocytes and PNS provided by Schwann cells
- In CNS one oligodendrocyte myelinates many axons, in PNS one Schwann cell myelinates only one axon
For each axon in the CNS and PNS, is myelin contributed to by just one cell or from many cells? (1)
Many
Describe the structure of a single sheet of myelin (including how many layers there are and how these layers sit in relation to each other). (3)
2 layers of myelin
Layers sit close together in middle
Around the edges, the layers are separated by cytoplasm
True or false? (1)
A single sheet of myelin is a little like ravioli - the layers are ‘stuck together’ at the edges and separated by substance towards the middle.
False - it is the opposite way round.
True or false? (1)
As the myelin wraps around an axon, the leading edge (which is the edge closest to the oligodendrocyte cell body) tucks underneath the existing layers of myelin.
False - The leading edge (which is the edge FURTHEST from the cell body), pushes under the rest of the myelin layers.
Which edge of the myelin sheet grows and forms new layers? (1)
a) the edge closest to the cell body
b) the edge furthest from the cell body
b) the edge furthest from the cell body
True or false? (1)
Looking at a transverse section of a myelinated axon right next to the node of Ranvier will show less layers of myelin than looking at a section of axon in the internodal region.
True - the inner tongue has a shorter width than the outer tongue because the sheet of myelin is not a perfect rectangle.
When looking at transverse sections of myelinated axons, what is happening at the intraperiod lines? (1)
The 2 outer faces of subsequent myelin wraps meet (one myelin sheet is stuck to a separate myelin sheet)
When looking at transverse sections of myelinated axons, what is happening at the major dense lines? (1)
The two inner faces of the same myelin sheet meet (where the two layers of one sheet are stuck together)
How does myelinating an axon affect capacitance? (1)
It reduces it
Is the relationship between membrane capacitance and number of myelin wraps linear? (1)
No - it is exponential
Does increasing the number of myelin wraps have more effect on membrane capacitance when there are more or less existing myelin wraps? (1)
Less
What is the meaning of the ‘g ratio’, in relation to myelin? (1)
The g ratio determines the optimal number of wraps of myelin.
Give the equation for the g ratio, and describe it in words. (2)
g ratio = di/do
Ratio of the axon diameter divided by the combined diameter of axon and myelin.
What does the value of the g ratio tend to be for central axons? (1)
0.75
True or false? (1)
Myelinating very small axons would actually slow down their conduction velocity.
True - however only very small axons
True or false? (1)
Increasing the diameter of unmyelinated axons is an efficient way to increase conduction velocity.
False - Increasing axon diameter in unmyelinated axons does not increase conduction velocity that much
Mammalian nervous systems would have much higher conduction velocities if all axons had large diameters and as many layers of myelin as possible.
Why doesn’t this happen? (2)
To keep the system compact.
And so that the brain doesn’t take up too much energy.
Give the two main components of myelin and their relative contributions. (2)
Predominantly fat
Some protein
Name the two main proteins found in CNS myelin. (2)
- MBP (myelin basic protein)
- PLP (myelin proteolipid protein)
Name the main protein found in PNS myelin. (1)
P0 (myelin protein zero)
You get given a sample of myelin to test in the lab without the originating glial cell. How do you tell if the myelin is from the CNS or the PNS? (1)
CNS myelin and PNS myelin differ in their protein composition.
What is the role of tight junctions in myelin? (1)
To stop current from leaking out of the axon between myelin layers.
In the axon-myelin partnership, give two places where tight junctions may form. (2)
- Between axon and myelin
- Between layers of myelin
Describe the distribution of voltage gated Na channels at the nodes of Ranvier. (1)
Concentrated at the nodes
Describe the distribution of voltage gated K channels at the nodes of Ranvier. (1)
Located at the juxtaparanodal and internodal regions.
Give two proposed roles of voltage gated K channels at the internodal regions. (2)
- Maintaining Vm at internodal region
- Preventing aberrant firing of the axon
If there are no voltage gated K channels at the nodes of Ranvier, how does repolarisation occur, and what differences are seen compared to areas which do have VGK channels? (2)
Repolarisation happens due to leak K channels.
The hyperpolarisation will be smaller.
Give three factors which affect the axonal conduction velocity. (3)
- Longitudinal resistance of axoplasm
- Capacitance of axon membrane
- Membrane resistance
Name a muscarinic antagonist. (1)
Atropine
Name a nicotinic antagonist. (1)
Curare
Which types of ACh receptors are present at the neuromuscular junction? (1)
a) nicotinic
b) muscarinic
Nicotinic
Name two AChE inhibitors. (2)
Eserine
Prostigmine
Give two effects of prostigmine on the action potential profile. (2)
- Larger response
- Longer-lasting
What is the difference between ‘current’ and ‘voltage’? (2)
Voltage is the difference in charge across the membrane.
Current is the movement of charge across the membrane.
Which occurs more rapidly at the neuromuscular junction after ACh release - current or voltage change? (1)
Current occurs quicker
Which of these statements is correct? (1)
a) the voltage across the membrane causes a change in current
b) the current across the membrane causes a change in voltage
b - the current across the membrane causes a change in voltage
Describe the difference between the end plate potential and the action potential at the neuromuscular junction. Describe how they are related? (4)
End plate potential is a depolarisation of the membrane
caused by ACh binding to receptors.
If EPP meets threshold, action potential is produced,
due to opening of voltage-gated Na channels.
Roughly what percentage of NMJ end plate potentials DO NOT result in an action potential? (1)
0% - the NMJ is a very reliable synapse
Complete the passage relating to MEPPs. (3)
‘MEPP’ stands for ……………………………
They occur due to ………………………………… at the NMJ.
MEPPs do not result in action potentials because ………………………………..
miniature end plate potential
spontaneous activity
they do not meet the threshold
What effect would curare have on the frequency and magnitude of NMJ MEPPs? (2)
Decreased frequency
Decreased magnitude
What effect would prostigmine have on the frequency and magnitude of NMJ MEPPs? (2)
Increased frequency
Increased magnitude
What effect would decreasing Ca have on the frequency and magnitude of NMJ MEPPs? (2)
Decreased frequency
No effect of magnitude
What effect would decreased Na have on the frequency and magnitude of NMJ MEPPs? (2)
No effect on frequency
Decreased magnitude
What is a quantum in general terms? (1)
A discrete, individual amount of a substance.
Describe the term ‘quantal release’ as it relates to neurotransmitters and MEPPs. (3)
A quantum can be referred to as the amount of NT in a single vesicle.
Each MEPP is due to release of a multiple of one quantum, ie. a certain number of vesicles being released.
Most MEPPs correspond to one unit of quantal release, ie. one vesicle being released.
In an MEPP, if one unit of quantal release causes a change in voltage of 0.4mV, what change would a triple quantal release cause? (1)
1.2mV
Describe how calcium causes presynaptic vesicles to release neurotransmitter.
What is this process called? (3)
Calcium causes proteins on the vesicles and membrane to interact.
This releases neurotransmitter
and is called synaptic docking.
Name four proteins which are required for synaptic docking. (4)
v-SNARE
t-SNARE
SNAP
NSF
ACh receptors are neurotransmitter-gated ion channels. Which ion/ions are ACh channels permeable to at the NMJ?
Na
K
If Vm of the membrane at the NMJ is negative, what will happen in terms of ion movement and currents when ACh channels open? (1)
Na moves in
If Vm of the membrane at the NMJ is positive, what will happen in terms of ion movement and currents when ACh channels open? (1)
K moves out
Describe what is meant by ‘habituation’. (1)
A reduction in response after experiencing repeated unimportant stimuli.
Describe the molecular process of habituation in a monosynaptic reflex. (2)
Decreased synaptic effectiveness between sensory and motor neurone,
due to decreased NT release from both sensory and motor neurones.
Describe the action potentials seen in sensory and motor neurones in the process of habituation in a monosynaptic reflex. (2)
Normal AP in sensory neurone.
Diminished AP in motor neurone.
Describe how the sensitivity of postsynaptic receptors is altered during habituation of a monosynaptic reflex. (1)
It is unaltered
What is meant by sensitisation? (1)
Repeatedly experiencing harmful stimuli leads to increased synaptic efficacy.
Give two examples of when sensitisation may occur. (2)
If a dangerous event has just happened, defence responses are enhanced.
If an injury has just occurred, responses to stimulation of adjacent skin are enhanced.
Which neurotransmitter is involved in short term sensitisation? (1)
Serotonin
Describe the molecular mechanism of short term sensitisation. (8)
Facilitating interneurone releases serotonin.
Serotonin binds to metabotropic 5HT GPCR on sensory neurone.
Binding of 5HT activates cAMP-dependent protein kinase A (via second messenger).
cAMP-dependent PKA phosphorylates certain K channels and closes them.
Reduced outward K current.
Prolonged AP, allowing more Ca to enter cell.
More NT release.
PKA also acts directly on vesicles.
What is classical conditioning? (1)
An animal learns to associate one type of stimulus with another.
Describe what is meant by the ‘unconditional stimulus’ in classical conditioning.
Give an example in Pavlov’s dogs. (2)
Stimulus will usually always evoke a response without requiring training.
Eg - food causes salivation
Describe what is meant by the ‘conditional stimulus’ in classical conditioning.
Give an example in Pavlov’s dogs. (2)
Will not usually cause the response unless training has occurred.
Eg - bell does not usually cause salivation
Briefly describe the process of classical conditioning. (3)
Conditional stimulus and unconditional stimulus are repeatedly paired.
Animal learns to associate them.
Conditional stimulus will then produce a response similar to that seen with the unconditional stimulus.
Describe the ideal timing of the pairing of the stimuli in classical conditioning. (2)
Conditional stimulus should precede the unconditional stimulus
by about 0.5 seconds.
Describe the molecular mechanism of classical conditioning. (5)
Conditional stimulus produces an action potential in the sensory neurone.
Calcium influx into presynaptic terminal.
5HT released by facilitating interneurone due to unconditional stimulus.
Because Ca is already in presynaptic neurone, the 5HT response is enhanced.
Presynaptic neurotransmitter release is enhanced.
In classical conditioning, how does calcium enhance the effect of 5HT on the presynaptic neurone? (3)
Calcium binds to calmodulin.
Calcium and calmodulin activates adenylyl cyclase.
More cAMP is produced.
Complete the sentence. (3)
Long term sensitisation and classical conditioning results from the production of new ……………… and ………………….., which is initiated and carried out by the action of repeated ………………………………
Proteins
Synapses
Short term sensitisation
In which part of the brain does long term potentiation occur? (1)
CA1 of the hippocampus
What is the function of long term potentiation? (1)
Memory formation
How is the fEPSP slope affected in CA1 neurones after LTP has occurred? (1)
It increases (gets steeper)
Which cells have to be stimulated to produce LTP in CA1 neurones? (1)
Schaffer collaterals
Give 3 requirements needed in CA1 for LTP to occur. (3)
CA1 neurone must have a large enough depolarisation.
Temporal summation.
Spatial summation.
Describe the molecular mechanism of LTP. (9)
Glutamate binds to AMPA receptors.
Na influx into cell.
Cell is depolarised.
Mg displaced and NMDA channel is opened.
Na and Ca enter through NMDA channel.
Ca activates protein kinase C and calcium calmodulin dependent protein kinase II (CaMKII).
Phosphorylation of AMPA receptors and increased number of AMPA receptors expressed on membrane.
Increased post-synaptic current.
Also retrograde signalling enhances presynaptic NT release.
Describe why a small presynaptic action potential will not cause a current to flow through postsynaptic NMDA receptors, and how a current CAN be produced. (3)
Mg blocks up NMDA receptors.
Mg is not displaced until the membrane is depolarised.
This is achieved through AMPA receptors.
AMPA channels are permeable to what ion/ions?
Na
K
NMDA channels are permeable to what ion/ions?
Na
K
Ca
NMDA channels are activated by glutamate, but they also have to be coactivated by which other molecule? (1)
Glycine
It is hypothesised that glutamate may also promote LTP by binding to metabotropic GPCRs. How do GPCRs help to promote LTP? (1)
Calcium release from endoplasmic reticulum.
Which one of these experiments has NOT been shown to produce deficits in LTP and memory in animals? (1)
- Knock out CaMKII gene
- Knock out NMDA receptors
- Knock out NMDA gene
- Knock out CaMKII gene
- Knock out calcium gene
Knock out calcium gene - there is no calcium gene you idiot.
