NEU 490 QUIZ 4 AP

Question 1

Receptor Potential - way we convert physical sensations into neuronal signals and sent by specialized sensory receptors

Difference between postsynaptic potential and receptor potential?

How do we convert physical sensations into neuronal signals?

Sensory nerve ending? These can be either what?

Ex Pacinian vibration detector?

slowly adapting vs rapidly adapting?

Answer 1

Difference between postsynaptic potential and receptor potential is there is no presynaptic neuron rather have an external stimulus which is processed by a specialized receptor this can either be a specific sensory organ that releases NT or a modified specialized nerve ending. Then in the sensory neuron have the receptor potential which can either be graded or can reach threshold to send an AP.

How do we convert physical sensations into neuronal signals? Specialized sensory receptors!

Sensory nerve endings: stimulus produces a local graded response that, if it is large enough, can lead to an action potential in the sensory neuron. These can be either due to neurotransmitter release from the sensory organ or can be a specialized nerve ending

Ex Pacinian vibration detector: pacinian corpuscles (mechanoreceptors sense vibration) - have lamale concentric receptors and then have nerve endings from primary afferent then when deformation happens from vibration then NA depo in nerve ending within and is referred to as receptor potential

Can be classified as slowly adapting(active duration of stimulus so continuous depo like merkel disks) or rapidly adapting(quick depo pulse for the start of the stimulus and an “off” response at end of stimulus - also called change detectors bc detect the change like Meisner)

Question 2

Synaptic Potentials - elicited by presynaptic input

Difference between synaptic and receptor potentials?

What type of potentials that occur in response to what?

Excitatory or inhibitory?

If an EPSP is?

PSPs:?

Answer 2

Difference between synaptic and receptor potentials is that synaptic are elicited by presynaptic input so transmitter binding to postsynaptic receptors on our postsynaptic neuron produces a postsynaptic conductance change as ion channels open or sometimes close in that postsynaptic membrane - these can be either excitatory(EPSP local depo) or inhibitory(IPSP local hypo)

Local graded potentials that occur in response to input from a presynaptic neuron, these are also called post- synaptic potentials

Can be excitatory or inhibitory, leading to either a local depolarization or hyperpolarization(depends on which specific ion channels activated in cell membrane - ex: inhibit NT can open that allow Cl into cell or metabolize something then inhibit like g-protein)

If an EPSP is large enough or is additive, can reach threshold and send an action potential - shift from graded potential to AP

PSPs: considered graded potentials bc amount of depo or hypo and how far it travels (local potentials)

Question 3

Summation of Postsynaptic potentials - can be added together to either increase or decrease the likelihood of AP which depends on kinetics and or location

Temporal summation:?

Spatial summation:?

Answer 3

Temporal summation: one presynaptic neuron - occur when rapid repetitive AP occurring in that same presynaptic neuron at the same location so a single neurons that has repetitive or strong stimulus - one presynaptic excitatory neuron
- Rapid repeat EPSPs same location (EPSP lasts a while)
- Add and sum to produce AP

Spatial summation: multiple presynaptic neuron - either two excitatory presynaptic neurons synapsing onto the same postsynaptic neurons or one excitatory and one inhibitory presynaptic neuron synapsing onto the same postsynaptic neuron - synapsing onto different parts of the postsynaptic close together still but in diff locations bc coming from diff presynaptic - these are multiple so can be simultaneous
- Simultaneous EPSPs in diff. parts of neuron
Add and sum to produce AP
- Simultaneous EPSP and IPSP in diff. parts of neuron
Add and reduce chance of AP

Question 4

Comparison of Temporal VS Spatial Summation

Sensory summation that involves?

presynaptic neuron how many?

Generates what?

Fast or slow?

Answer 4

Temporal Summation:
- Sensory summation that involves the addition of single stimuli over a short period of time
- A single presynaptic neuron is responsible for generating the action potential
- One presynaptic neuron generates sub thresholds over a certain period of time - added together
- A less efficient process as it takes time to generate an action potential

Spatial Summation
- Sensory summation that involves stimulation of several spatially separated neurons at the same time
- Multiple presynaptic neurons are responsible for generating the action potential
- Multiple presynaptic neurons generate sub thresholds
- More efficient - faster

Question 5

Passive(graded potentials) and Active Electrical Responses (action potentials)

Neurons translate a graded signal into an?

AP overcome the problems of?

Information(strength of stimuli) is then contained in the?

NT secretion:?

Increasing stimulus strength is coded with increasing?

DON’T CHANGE SIZE OF AP INSED CHANGE ?

Answer 5

Neurons translate a graded signal into an “all or nothing” signal, the AP

AP overcome the problems of passive conduction over long distances - avoid decay of the signal

Information(strength of stimuli) is then contained in the frequency and timing of the AP, as well as which axons are firing(myelinated vs unmyelinated axons and inhibition vs excitation neurons) - instead of coding info based on size AP we code with frequency

NT secretion: with greater stimulus intensity see greater increase AP frequency this leads to increase in NT secretion(which will affect the next postsynaptic neurons) and more vesicles of NT for larger stimulus

Increasing stimulus strength is coded with increasing frequency of AP so size does not change but the frequency changes with stimulus intensity - not only changings in the frequency of AP but changes in amount of NT secreted at axon terminals

DON’T CHANGE SIZE OF AP INSED CHANGE THE FREQ based on stimulus intensity then we pass on that info about stimulus intensity by changing the amount of NT that we secrete so secrete more vesicles of NT for large stimuli

Question 6

A postsynaptic neuron has three other neurons that synapse onto it, with synapses located nearby to each other. Two are excitatory, and one is inhibitory. The first presynaptic neuron elicits an EPSP of +5mV The second presynaptic neuron elicits an EPSP of +14mV The third presynaptic neuron elicits an IPSP of -10mV

What type of summation is this?

What is the new membrane potential?

Will the postsynaptic neuron send an action potential?

Answer 6

What type of summation is this? Spatial

What is the new membrane potential? 5+14-10=9 then -70+9=-61mv

Will the postsynaptic neuron send an action potential? no

Question 7

If the neuron is depolarized enough to reach a threshold, what needs to occur in order to send an action potential?

Answer 7

VG Na channels need to open, allowing Na to rush in

Question 8

The Action Potential?

Steps of the Action Potential which four?

Answer 8

Small changes in membrane potential (graded potentials) can be depolarizing or hyperpolarizing.

A depolarizing potential that exceeds a threshold becomes an action potential.

Steps of the Action Potential
- Rest: at rest membrane permeability is more for K then Na
- Rising Phase: Depolarization
- Falling Phase: Repolarization
- Hyperpolarization and Recovery

Question 9

Ion Channels: Voltage-sensitivity and Ion Selectivity

Ion channels: ?

Different gating mechanisms:
- Resting K leak channel?
- VG?
- Ligand?
- Signal?

Selectivity filter allows for?
Molecular gate excludes non favored ions by:?

Answer 9

Ion channels:
Pores in the cellular membrane that allow the passage of ions across the impermeant lipid cell membrane. A way for polar ion molecules to cross

Different gating mechanisms:
- Resting K leak channel: always open
- VG: opens transiently in response to change in the membrane potential, most important type for AP
- Ligand gated: opens closes in response to a specific extracellular NT
- Signal gated: opens closes in response to a specific intracellular molecule for example g-protein - most important in postsynaptic

Selectivity filter allows for flux of a particular ion
Molecular gate excludes non favored ions by:
Size
Charge
Hydration

Question 10

Voltage-gated Channels - electrically driven movement of the voltage sensory
— How do channels open at certain voltages

Ion channels have four what? displaying what?

Voltage sensor is where and has what?

What leads to a conformational change?

Confirm importance of positive chargers by replacing with? Name of model?

steps 1-4?

Another model is the paddle model - instead of the?

Answer 10

Ion channels have four homologous domains, each displaying six transmembrane alpha - helical segments domain. - Resting voltage sensory and pore domain are one domain

The fourth transmembrane segment (S4 - voltage sensor) has four to seven positively charged amino acids - usually arginine

These positive charges are repelled by depolarization of the membrane, leading to a conformational change in the ion channel and opening the pore to allow ion flow.

Confirm importance of positive chargers by replacing with neutral amino acids then saw loss of voltage selectivity so instead of opening at a more positive voltage could always open or either never opened - The sliding Helix model: there are multiple models

1. • charges in S4 serve as gate
2. S4 remain in membrane doesn’t leave merely moves
3. S4 moves outward and rotates
4. • chargers in the S4 segment form ion pairs with negative charges in neighboring segments

Another model is the paddle model - instead of the transmembrane staying upright and going up and down instead are on the side of the membrane and instead of swing up and to the side

Question 11

Ion Selectivity Filters

Potassium channels exhibit an unusual selectivity, allowing passage of larger K+ ions over smaller Na+ ions – how does it do this?

Selectivity filter (sf) lined with?

K sheds?

Answer 11

Potassium channels exhibit an unusual selectivity, allowing passage of larger K+ ions over smaller Na+ ions – how does it do this? – + charger ions through and four inner helices come together near surface fined with negatively charged AA negative plus ions are attracted

Selectivity filter (sf) lined with polar atoms that are very narrow and ions must be dehydrated before entering it

K sheds H20 and interacts with oxygens and spatially proximity and repelling and fast moving through channel - fast trajectory and fast passage

The selectivity filter is so narrow that the ions must first be dehydrated before entering it. Potassium is typically cushioned by water molecules while in solution, and when passing through the channel, potassium sheds its water shell and interacts with the channel oxygens, which are perfectly spaced to mimic this shell.

Sodium ions are too small to interact with these oxygens in the same way, instead staying cushioned by their own water shells outside the channel pore. - or if shed H20 then move through channel in slow and tortious trajectory

Na can not pass through K channels due to differences in the selectivity filter and the binding sites within the channel. The channel for out K channels first allow just cations to move through positive chargers ions due to the four inner helices that come together near the surface and are lined with negatively charged amino acids this always for a high concentration of cations near the membrane then anions bc of the opposing chargers so positive ions are attracted. Select for K and not Na bc both are charged this is through Selectivity filter which also known as SF is lined with polar atoms very narrow and ions must be dehydrated before entering it (K is by 4 water molecules so when K pass through channel it sheds the water molecule and interacts with the channel oxygen). Na has a tortious trajectory(only binds to 2 oxygens so bounce from side to side) and slow elution - can pass through K channel but not that much.

Question 12

Change in Ion Permeability During the Action Potential

Depolarization phase: ?

Repolarization phase: ?

Hyperpolarization phase: ?

Answer 12

Depolarization phase: Due to large increase in membrane permeability to sodium - bc opening VG Na channels so Na flood in

Repolarization phase: Due in part to a drop in sodium conductance due to inactivation
Largely driven by the increase in membrane permeability to potassium due VG K opening - Na close K open and flood out

Hyperpolarization phase: Due to continued conductance through delayed rectifier potassium channels

Question 13

Question: Black mamba snakes have a poisonous venom named dendrotoxin. Dendrotoxin binds to voltage gated potassium channels, blocking their activity. How would this affect a neuron treated with dendrotoxin?

Question: Tetanus is an infection caused by the bacterium Clostridium tetani. People infected with tetanus experience extremely painful muscle spasms typically in the jaw and neck, but severe infections can affect all muscles of the body. Which of the following might be a way in which the tetanus toxin causes muscle spasm (Select all that apply)?

Answer 13

The cell will initially depolarize but repolarization will take much longer.

Greatly increase the permeability of the presynaptic ACH neuron to Na at rest AND block the fusion of GABA filled vesicles to the presynaptic cell membrane of interneurons.

Question 14

Voltage-gated Sodium Channel Inactivation

Inactivation of VGSCs serves a critical determinant of ?

fast inactivation in VGSCs occurs within a few? Fast inactivation serves as a?

There are several potential models for voltage-gated sodium channel inactivation, including the?

Fast inactivation is produced by a block of the internal ?

During inactivation the inactivation particle most likely forms a?

Without inactivation go to equilibrium potential for?

Answer 14

Inactivation of VGSCs serves a critical determinant of neuronal excitability.

First described by Hodgkin and Huxley, fast inactivation in VGSCs occurs within a few milliseconds of opening. Fast inactivation serves as a negative feedback switch. Abnormalities can lead to physiological dysfunction.

There are several potential models for voltage-gated sodium channel inactivation, including the ball-and-chain model and the hinged-lid model

Fast inactivation is produced by a block of the internal vestibule(pore in the intracellular side) by a tethered inactivation particle that has been mapped to the internal linker between domains III(3) and IV(4) of the channel.

During inactivation the inactivation particle most likely forms a hydrophobic interaction with an inactivation gate recep

Without inactivation go to equilibrium potential for Na

Question 15

Delayed Rectifier Voltage Gated Potassium Channel (there’s a whole family of them)

Delayed outward current and slow activation gate closing leads to?

Voltage-gated potassium channels form a large and diverse family that is evolutionarily conserved. There are ?

The delayed rectifier potassium channels are a family of potassium channels (WHICH channels?) that allow a sustained K+ efflux with a delay after membrane WHAT? The outflow of potassium ions rapidly WHAT the membrane. - continued flow bc of slow gate then WHAT???

Channel activation:
Delayed channel opening with?
Channel gates closed slowly with ?

TEA is what?

Answer 15

Repolarization during AP is delayed outward current and slow activation gate closing leading to hypo

Voltage-gated potassium channels form a large and diverse family that is evolutionarily conserved. There are 40 human voltage-gated potassium channel genes belonging to 12 subfamilies.

The delayed rectifier potassium channels are a family of potassium channels (Kv2 channels) that allow a sustained K+ efflux with a delay after membrane depolarization. The outflow of potassium ions rapidly repolarizes the membrane. - continued flow bc of slow gate then hyperpolarization

Channel activation:
—- Delayed channel opening with depolarization – requires more positive membrane to move the voltage sensor
— Channel gates closed slowly with repolarization

Tetraethylammonium (TEA) blocks delayed rectifier

Question 16

Refractory Periods General which 3?

Absolute refractory period: ?

Relative refractory period: ??

Answer 16

General:
- Limits maximum frequency of AP trains
- Prevents AP from traveling backwards
- As they regeneratively travel down an axon, each AP is followed by a refractory “wake”

Absolute refractory period:
— Gna(sodium conductance) is inactivated, and it is physically impossible to produce another depolarization. - Na conductance is inactivated so no matter how powerful stimulus - Do not have multiple APs on top of each other
—- Removal of the Gna inactivation state requires a return to subthreshold Vm. - have to go below -55mv to close

Relative refractory period:
— Enough Gna (sodium conductance) are available to produce an AP.
— Physically more difficult to achieve threshold because Vm is more negative than RMP (due to increase in Gk during the hyperpolarization)
— Ionic conditions continuing to be reset by the sodium/potassium pump
— Would need greater depo from postsynaptic input

Question 17

Acquired neuromyotonia (Isaac’s syndrome) is considered to be an autoimmune disease, and the mechanism of nerve hyperexcitability in this syndrome is correlated with anti-voltage-gated K(+) channel (VGKC) antibodies. Research: how does potassium channel dysfunction lead to neuromyotonia?

Another type of potassium channel is considered inwardly rectifying, meaning that potassium actually flows into the cell through this channel. What do you anticipate is the function of this channel?

Answer 17

Effects delayed rectifier K channel
Prolong the AP - the ability to send multiple AP is primarily driven by Na conductance as a long as were below threshold so VG Na can repone
Prolonged AP will have prolonged depolarization of axon terminal and VG then Ca channels stay open longer and more vesicle recruit and more NT release
Neuromyotonia synonyms can be cramping, sweating increased heart rate, and muscle twitching bc overactivation (fasciculations) - too much NT release

Control K ECF concentration to protect from hyper excitation and get back to RMP

Question 18

K+ Homeostasis

Accumulation of K+ in which space?

K homeostasis that astrocytes do either K driven?

Important characteristic of the inwardly rectifying channels is that when we increase extracellular concentration of K this alters the ?

Role of Astrocytes in K+ Homeostasis:
A and B?

Answer 18

Accumulation of K+ in extracellular space is a normal consequence of electrical activity of neurons

K homeostasis that astrocytes do either K driven into the cell when there’s an excess concentration they primarily go in through the inwardly rectifying K channels or can have K spatial buffering where through gap junctions that K could travel from astrocyte to astrocyte until we reach an area that has lower ECF concentration of K

Important characteristic of the inwardly rectifying channels is that when we increase extracellular concentration of K this alters the IV plot - normally curve is to the left so when increase K curve shifts to the right - cations go into the cell below the K and go out cell above K - shift in concentration the inwardly rectifying channels are sensitive to this

Role of Astrocytes in K+ Homeostasis:

a) Na+ /K+ ATPase - uptake in astrocytes 5-fold higher than in neurons - pumps K in and Na out

b) K + channels (Kir4.1; possibly rSloKCa channels) - Kir4.1 inwardly rectifying K channel and K flows into cell bc sensitive to changes in extracellular concentration of K

Question 19

Kir4.1

expressed predominantly in ?

Allow large inward K+ currents at?

Dysfunction of these channels can predispose the cell to ?

Answer 19

expressed predominantly in brain astrocytes and retinal Muller cell (radial glia - astrocyte subtype)

Allow large inward K+ currents at potentials negative to EK and small, but significant, outward K+ currents at those positive to EK

Dysfunction of these channels can predispose the cell to hyper-excitability - seizures

Question 20

Passive Conduction down Axons?

Active Conduction down Axons?

What membrane properties affect decay??

Answer 20

Passive conduction decays over distance due to leakage of current across the membrane - how far current will spread down the length for different things that can affect how much were going to decay down the length of the membrane

Active conduction is constant over distance, regenerating along the length with VG channels

What membrane properties affect decay??
No VG you just have a membrane of a cell and you inject current you will see decay over time and length based on the properties of that membrane

Question 21

Resistance to flow of ions – How difficult it is for ions to move

Membrane Resistance =?

More channels =

High membrane resistance =

Low membrane resistance =

Unmyelinated has?

Higher membrane resistance = faster or slow what

Lower membrane resistance = faster or slow what

Answer 21

Membrane Resistance = number of open channels - Rm - Membrane resistance how hard it is to move through the membrane

More channels= less membrane resistance

High membrane resistance = myelinated

Low membrane resistance = unmyelinated

Unmyelinated has leak channels that are uncovered and able to have ions moving across the membrane

Higher membrane resistance = faster AP conduction velocity

Lower membrane resistance = slower AP conduction velocity - bc more leakage

Question 22

Internal resistance =

The diameter of the axon determines the amount of?

Larger/wider =

Smaller diameter axon =

Higher internal resistance = slower or fast what

Lower internal resistance = slower or fast what

Answer 22

Internal resistance = diameter of axon

The diameter of the axon determines the amount of space

Larger/wider = less internal resistance - Ri or Ra(axoplasma)
– Fewer collisions with membrane
– Less likely to bump and hit leak channel but more likely for more Na ions to make it down to the next segment to open up our next VG Na channel

Smaller diameter axon = have higher internal resistance bc resistance is how hard it is to move through axon

Higher internal resistance = slower AP conduction velocity

Lower internal resistance = faster AP conduction velocity

Question 23

Capacitance - two plates that can store charge

Capacitor: ?

Buildup of - charge on the inside ?

Hard to get incoming Na + charges to ?

Fix this by?

Higher CM =

Lower CM =

Larger plated =

Further away =

Answer 23

Capacitor: devices where equal and opposite charges are held on separate “plates”, with a potential difference between them proportional to this charge - further way plates the lower capacitance and larger plates are the larger capacitance - larger cell will have greater cap but there is a limit

Buildup of - charge on the inside membrane due to close proximity of + and – charge on either side

Hard to get incoming Na + charges to move along instead of gathering around – charged ions at membrane

Fix: Add myelin to increase distance between + and – charge at rest
charges inside won’t line up as heavily

Higher CM = slower AP conduction velocity

Lower CM = faster AP conduction velocity

Larger plated = larger CM

Further away = lower CM

Unmyelinated stretches of axon we have less distance between positive charges on the outside of the membrane and the negative charges in the inside of the membrane so greater level of attraction so pull Na+ in but in myelinated you increase the distance between plates so there is a weaker attraction between those positive chargers on the outside and the negative charges inside - the negative charges have a weaker pull to go towards membrane so they pull of cations being attracted so lose less Na ions being attracted to those anions lined up against the membrane bc the anions aren’t super tingly lined up against membrane so weaker attraction to the positive charges on the outside of the membrane

Question 24

1. Large diameter axons have ____________ (higher or lower) internal resistance compared to small diameter axons. If the internal resistance of an axon is high, this will _____________ (increase or decrease) the velocity of the action potential compared to an axon with low internal resistance.
2. Unmyelinated axons have __________ membrane resistance than myelinated axons. This is due to greater _________________.
3. How does membrane permeability to K+ (PK ) and Na+ (PNa) change during an action potential?
4. The refractory period is responsible for what other principle of action potentials?

Answer 24

1. Answer: Lower; decrease
2. Answer: Lower; leakage of ions across the membrane
3. Answer: PK exceeds PNa at rest; PNa temporarily increases during the action potential.
4. Answer: Forward movement

Question 25

Time Constant –> smaller time constant =

The time constant is the time it takes?

The smaller the time constant, the more rapidly a ?

Therefore, the smaller the time constant, the more rapid ?

Equation:
T (time constant) =

Answer 25

Time Constant –> smaller time constant = fast AP velocity

The time constant is the time it takes the membrane potential to reach 63% of its final value.

The smaller the time constant, the more rapidly a depolarization will affect the adjacent region. If a depolarization more rapidly affects an adjacent region, it will bring the adjacent region to threshold sooner.

Therefore, the smaller the time constant, the more rapid the propagation velocity.

Equation:
T (time constant) = TM(resistance of neuron membrane) times CM (capacitance of neuron membrane)

Question 26

Length Constant –> length constant high =

Lambda is how well ?

Membrane potentials decay exponentially with?

Space or length constant is an index of how well a ?

The greater the value of the length constant, the?

A large length constant can contribute to?

This is how we sum or EPSP to produce an?

Equation: Lambada =

Answer 26

Length Constant –> length constant high = more efficient so faster AP

Lambda is how well does the membrane spread down the length of the axon so how far before it decays

Membrane potentials decay exponentially with distance.

Space or length constant is an index of how well a potential will spread along an axon as a function of distance – it is the distance at which the potential is 36.8% of the maximal value

The greater the value of the length constant, the farther the potential will travel.

A large length constant can contribute to spatial summation - the electrical addition of one potential with potentials from adjacent areas of the cell. - easier for a postsynaptic neuron to reach threshold bc easier fro that neuron to add up all the stuff from multiple presynaptic neurons that are farther apart

This is how we sum or EPSP to produce an AP and how we ensure proper spreading of our depo down the length of the axon inorder to reach the next VG channel

Equation:
Lambada = square root of (Tm/Ti) (resistance of neuron membrane/internal neuron restsince)

Question 27

What are things that can affect Time and Length Constant?

Diameter: Increase diameter
Rm(membrane resistance)=
Ri (internal) =
Cm=
T=
Length =

Myelin - myelinated a neuron
Rm =
Ri =
Cm =
T =
Lambda =

Equations:
T =
Lambda =

Small capacitance (thickly myelin axon) =

High Cm in unmyelinated =

Answer 27

Diameter:
Rm(membrane resistance)= unchanged
Ri (internal) = deceased
Cm= unchanged
T= no change
Length = constance increase

Myelin:
Rm = increase
Ri = unchanged
Cm = decrease
T = unclear
Lambda = increase

T=Rm x Cm

Lambada = square root of (Tm/Ti) (resistance of neuron membrane/internal neuron restsince)

Small capacitance (thickly myelin axon )= faster velocity

High Cm in unmyelinated = slower velocity

Question 28

Which of the statements is False?

A) High axonal (internal) resistance (Ri) impedes current spread thereby decreasing the speed of the action potential

B) Myelin increases the length constant, allowing for longer propagation of the action potential. - if you add myelin too unmyelinated axon

C) Velocity of action potentials is inversely proportional to capacitance of the membrane (Cm).

D) High membrane resistance (Rm) results in current leak thereby decreasing conduction velocity.

E) None are False

Answer 28

ANSWER D) High membrane resistance (Rm) results in current leak thereby decreasing conduction velocity.

Question 29

Which statement is FALSE?

a) Myelin increases membrane resistance (Rm).

b) Myelin has no effect on the internal resistance of the axon (Ra or Ri).

c) Saltatory conduction is transmission of an action potential down an axon through depolarization at nodes of Ranvier.

d) Myelin increases the length constant by decreasing membrane capacitance (Cm).

e) An “ideal neuron” would have an infinitely high length constant and an infinitely low time constant.

Answer 29

ANSWER d) Myelin increases the length constant by decreasing membrane capacitance (Cm).

Question 30

1. Where in the neuron are VGSCs typically located? Does this differ between a myelinated versus unmyelinated axon?
2. How do VGSCs function in the production of an action potential? What role do they play in generating and propagating action potentials?
3. What are characteristics of the epileptic brain?

Scn1a Knockout Model – These are mice with a null mutation in Scn1a. That means that the mutation causes the gene to be totally dysfunctional, and no proteins (channels) are made in the body.
Het -?
WT -?

Scn1a R1648H Mutant Model – These are mice with a missense point mutation in Scn1a. A missense mutation results in the substitution of an amino acid, but the entire protein is still produced. However, the substituted amino acid can result in a changed structure and function of the protein.
WT - ?
Het - ?
Homozygous RH -?

1. Which of these mutations (the knockout (KO) or the RH) do you predict to result in a more severe phenotype (increased seizure frequency and even mortality)? Why?
2. What effect do you think an altered amino acid in the voltage sensor of the sodium channel will have?

Part 3: Sodium Channels and Action Potentials
KO - ?
Het ?
Homo 2 -?
Het - ?

Part 4: The Final Enigma
Less inhibition - so decrease burst of activity GABA interneurons
Gabaergic interneurons
Pyramidal neurons

Look at photos from slides and then look at pain class photos for less inhibition and that seesaw

Answer 30

1.VGSCs myelinated at nodes of ranvier and in unmyelinated VGSCs down entire length of axon bc if not down entire length then decay and at dendrite only have an initial one not down whole length but then that signal is going to decay versus being boosted

2. Opening of VG Na channels leads to depo and they open bc of the voltage sensor located on the 4th transmembrane out of 6 total, voltage sensor is made up of positively charged amino acid(AA). Voltage sensory and charged AA causing a conformational change making a pore allowing ions to move through at -55
3. many times medial temporal lobe is where seizures occur example HM - hyperexcitability

Het - half the normal amount of SCN1A
WT - normal amounts of SCN1A

WT - normal SCN1A
Het - half of SCN1A has mutated voltage sensor
Homozygous RH - all of SCN1A has mutated voltage sensor

1. KO non is better than altered
2. Affecting inactivation maybe will stay open or close either way or easier/harder to open could change threshold or could not open at all so nonfunctional or no effect

KO - deadly
Het lots of seizures
Homo 2 - seizures die before 26 days
Het - infrequency spontaneous seizures

Question 31

should know which flows in and out for AP

Answer 31

LOOK AT PHTOT IN SLIDES