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228 Cards in this Set
- Front
- Back
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What is the relationship between temperature and diffusion? |
As temperature increases, diffusion increases. |
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If you have + and - on one side of a membrane, and you insert a + channel and increase the temperature what will happen? |
The amount of + ions that go over will be more compared to at lower temps. |
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If you have + and - on one side of a membrane, and you add a big negative charge to the other side and a + channel? |
+ ions will be pulled over; we can calculate how many with the Nernst Equation |
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Nernst Equation |
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Is the Nernst Equation about all the ions or just a single ion? |
The Nernst Equation is just about a single ion.
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What is Veq in the Nernst Equation and the units for it? |
Equilibrium Potential; volts |
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What is R in the Nernst Equation? |
Gas Constant |
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What is the T in the Nernst Equation? |
Temperature |
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What is the z in the Nernst Equation? |
Ion charge (often 1, -1, or maybe 2) |
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What is the F in the Nernst Equation? |
Faraday's Constant aka how much charge can go into a capacitor. |
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What is [X]out/[X]in in the Nernst Equation? |
Concentration of the ion outside / Concentration of the ion inside |
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Nernst Equation in Words |
Equilibrium Potential (Volts) = [ Diffusion / ( Ion Charge x F ) ] ln ( out / in ) |
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What is the relationship between Temperature and Voltage? |
As temperature increases, voltage need increases (can build up higher voltage at higher temperature) Double check this? |
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What is the relationship between Ion Storage in Capacitor and Voltage? |
The more ions able to be stored in capacitor = brings the voltage need down resulting in smaller voltage. |
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Goldman Equation |
The Nernst Equation applied to many ions at once; just apply voltage (z) to each ion in/out pair and multiply each by p (their permeability). |
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What causes membrane potential? |
You need the Na+/K+ ATPases to create the concentration of ions (Na+ and K+) inside vs. outside, but if you could create these concentrations another way you wouldn't need the ATPases. However, the most important part is passive ion channels that only pass some ions. You need these channels so ions cross and build up charges creating membrane potentials. |
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The membrane is a _________. |
Capacitor |
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Practice using Nernst equation
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Just do this... |
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Depolarization |
Increase from -70 membrane potential. |
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Hyperpolarization |
Decrease to -70 membrane potential. |
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Driving Force |
The difference between the resting potential and the membrane potential that drives the movement of ions. |
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Membrane Capacitance: Does current speed up or slow down over time? |
Slows down; exponential decay. |
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Membrane Capacitance: Does voltage increase or decrease over time? |
Increases (builds up); exponential growth. |
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The product of resistance and capacitance = |
Time constant. |
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Ohm's Law |
Voltage = Current X Resistance |
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Resistance Units |
Ohms |
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Voltage Source Units |
Volts
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Current Units |
Milliamps |
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Variable for Current |
I |
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Adding resistors together results in _______ conductance. |
decreased |
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3 Rules of Adding Resistors |
1. The voltage drop (in total) has to be equal tothe volts of the voltage source. 2. The current flow (through each) has to be thesame (since each electron has to go through both resistors) 3. Therefore, two 100 Ohm resistors is equivalentto having one 200 Ohm resistor |
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The Math of Adding Resistors |
Req = R1 + R2
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Parallel resistors results in _______ conductance. |
increased |
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Why do parallel resistors decrease resistance? |
The ions have two resistor options, so this decreases the total resistance.
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The total current before or after the resistors must be equal to... |
the sum of the current in the resistors. (?) |
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The Math of Parallel Resistors |
Add the Inverses 1 / Req = 1 / R1 + 1 / R2 |
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Conductance is... |
the inverse of resistance. |
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Resistance _____ current flow. |
slows |
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Conductance is the ability for ____ to _____. |
currents/ions; flow
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Capacitor |
Charge storing device. |
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What is a capacitor made up of? |
Two metal plates around an insulator. |
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What does a capacitor look/work like? |
A membrane. |
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What does a capacitor do? |
It stores charges on either side of the insulator. When you connect it to a circuit is adds electrons to the negative end and takes them from the positive end. As the charges increase, it makes it harder for additional charge to be stored. |
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Variable for Charges |
Q |
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Capacitance |
The amount that can be stored in a capacitor. |
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Capacitance = |
Charge / Voltage |
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Capacitance Units |
Farad |
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Charge Units |
Coulomb |
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Capacitor Series Math |
1 / Ct = 1 / C1 + 1 / C2 |
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Capacitor Parallels Math |
Ct = C1 + C2 |
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Series capacitors make capacitance... |
go down. |
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Parallel capacitors make capacitance... |
go up. |
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Current speed decreases over time (exponential decay). |
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Voltage builds up over time (exponential growth). |
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R = Resistor I = Current V = Voltage E = Equilibrium Potential (?) |
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Nernst Equation: zF |
Capacitance |
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Bigger difference in concentration ration in Nernst Equation means... |
the more strongly diffusion tries to force molecules across and the bigger the Veq will be. |
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What happens when [X]in is higher than [X]out in the Nernst Equation? |
You get a negative Veq. |
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What is Veq?
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Veq is like how much the ions are forcing themselves through. |
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Higher Veq is caused by... |
more force (higher resistance).
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Lower Veq is caused by... |
less force (higher capacitance). |
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Be able to use... |
Goldman Equation. |
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Membrane Potential is caused by...
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ion concentrations differing across the membrane and the permeability of the membrane to each of the ions being different (selective channels). |
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Membrane potential is not caused by... (3) |
1. Charge imbalance 2. Anchored anions 3. Not directly because of Na+ K+ ATPase |
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Do a lot or just a few ions have to cross to cause membrane potential to hit that ions equilibrium level? |
Just a few; a negligible amount and this is why the concentrations don't change when action potentials occur. |
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What happens when you connect the battery to the capacitor? |
The battery starts charging the capacitor. At first the current is strong, but it diminishes over time. In the mean time voltage goes from nothing to charging the capacitor up to the voltage of the battery. |
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Time Constant |
How long it takes to decay 37% (1/8) of the original. Takes the time of RC. |
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Time Constant = |
Resistance X Capacitance, so when you mess with resistors and capacitors you can change how long it takes to decay. |
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Top - Extracellular Bottom - Intracellular 1 Capacitor (emulating membrane capacitance) 3 Batteries Equilibrium Potentials for each of 3 main ions; Potassium and Chloride (-) and Sodium (+) E = Equilibrium Potentials |
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1/G(ion) |
What is G? How we talk about resistance of membrane to ions. |
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1/R = |
Conductance |
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1/C = |
Resistance |
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Goldman Equation Simplified |
Vm = Equilibrium Potential / Conductance We can measure these to determine membrane potential. |
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Graded Potential |
Measure electrical response with 3 recording electrodes and 1 stimulating electrode. Deliver current pulse and the capacitor charges up nearby, but the further it goes the effect fades out. This leads into Length Constant. |
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Length Constant |
X; how far a (current?) gets before it decays. When a current is in the cell some will leave and some will move through the cell. How much eaves and how much moves through the cell this affects the length constant. |
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Lower the membrane resistance and... |
more current leaks out, so it decays faster resulting in a shorter length constant. |
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Length Constant vs. Circuits |
You get the same exponential decay you had with time constant. |
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Meaning? |
Tells you Voltage at distance of X related to the initial voltage. |
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Variables meanings? |
Rm = membrane resistance per unit area of surface Ri = internal (axial) resistance per unit area of surface d = diameter of fiber Vo = initial voltage X = length |
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Length Constant (equation) |
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Higher length constant = |
faster voltage spread through neuron. |
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How do you get a higher length constant? 3 ways. |
1. Increase diameter of axon 2. Increase membrane resistance 3. Decrease axial resistance |
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Which is stronger, membrane resistance or axial resistance? |
membrane resistance >>> axial resistance |
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Length Constant and Speed |
Longer length constant gets the signal there faster, but not because it is sent faster rather because it gets further in the same amount of time. |
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What happens when you inject ions into an axon? |
They quickly quickly redistribute in all directions ( a couple even leave). |
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Great Length Constant = |
20 mm |
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Normal Good Length Constant = |
2 mm
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Do graded potentials have good length constants? |
Not really. they don't send great messages because they decay so quickly. This is why they use action potentials instead. |
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What cells have action potentials? |
Muscle cells and neurons. A couple additional kinds of cells have action potentials in animals, but we won't worry about them. |
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Where does the AP occur? |
Not really in dendrites or soma. Starts at axon hillock and travels down the axon. |
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First Action Potential Experiment |
Took Sodium out of water surrounding (neuron?). Saw the action potential decreased. Concluded Sodium must be critical to the AP. Read more about this in book. |
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Electrically you can change... |
current, resistance, and capacitance. ? res is what does change ? |
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Voltage Clamp
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Holds voltage constant. You can inject current if the current is changing to maintain this constant voltage. |
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What does a voltage clamp let you measure? |
How much current you inject to maintain voltage helps you figure out resistance with Ohm's Law. |
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Inward Current |
Positive ions moving in (or Negative ions moving out). |
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AP under voltage clamp shows an inward current followed by an outward current. |
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Outward Current |
Negative ions entering or positive ions leaving. |
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When you replace Na with Choline, which cannot cross membranes in the Voltage Clamp experiment you see... |
The inward current is eliminated, but the outward current remains (blue line). |
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Results of the Voltage Clamp Experiment (2) |
1. Shows there is 2 parts to the action potential.
2. Sodium and Potassium are involved. |
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3 (4) Main Voltage Phases of an AP
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1. Rising phase (Na) 2. Falling Phase (K) 2.5 Undershoot (not in all AP) 3. Refractory Period (reset for next AP) |
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AP and Equilibrium Potentials |
Top: Sodium Equilibrium Potential (40) Middle: Membrane Potential (-70) Bottom: Potassium Equilibrium Potential (-95) |
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Does the AP reach Na and K equilibrium potentials? Why or why not? |
No, it just gets close. To hit the equilibrium potential you would have to have 0 permeability for all other ions, which would not happen. |
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Other names for Equilibrium Potential |
Nernst or Reversal Potential (because it is the point where the current reverses and goes the other way again because equilibrium has been reached) |
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What is driving force? |
It is a number!! |
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Higher driving force = |
more/faster movement of ions. |
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Why is there a slow build up before the fast AP? |
R starts big and ends small. When R is big it is slow. When ion channels open the R drops drastically thereby changing the time constant and making it much faster.
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Is membrane capacitance fixed? |
Yes but resistance changes. |
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What happens if voltage gated K+ are NOT delayed in opening (they open when Na+ channels open)? |
Just something to think about. |
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Some Qualities of APs (4) |
1. They are all or none 2. They are always the same in the same neurons 3. You can do lots of them in a row (regenerative) 4. The are unidirectional (unless initiated non-physiologically in the middle of the axon and then they shoot both ways). |
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Molecular Basis of APs?
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Channels are voltage gated. They have rapid inactivation (open, close, lock for refractory period). They have selective ion channel conductance (toxins often bind to these channels). |
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How did we find voltage gated channels? |
They only exist in nodes between myelin in human neurons, so very hard to locate. However, electric eels shock with ion gated channels, so they have many and we were able to purify and observe these channels from eels. |
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Ion Channel Structure |
6 Parts X 4 |
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How many passes are there in ion channel structure? |
6 |
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How many domains are there in ion channel structure? |
4 |
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What do passes 1-4 do? |
This is where the voltage sensor is. When the inside gets positive, it pushes pass 4 up which pulls at 5 and 6 causes them to twist open.
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Which ion channel pass has charges attached to it? |
#4 has positive charges |
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How do ions pass through ion channels? |
They go through 5/6 on two structures that loop together to make a heart like structure; ions pass through the center of the heart. |
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How do ion channels have selectivity? |
Passes 5/6 loop and that loop causes selectivity. Size is critical for selectivity. |
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What do the intracellular loops do in ion channels? |
They cause inactivity. True, but how? |
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Ball and Chain Model |
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Top: our stimulation; 1 ms then 6 ms Middle: Neuron 1, has one action potential per stimulation Bottom: Neuron 2, has one action potential for first stimulation then 3 in a row for longer stimulation Explanation: Neuron 1 has a much larger refractory period. Neuron 2's period of inactivation is much shorter; its inactivation gate is closed for a much shorter period of time than neuron 1's. |
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Current vs. Voltage
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Current = charge Voltage = difference in charge (?) |
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Relationship between Undershoot and Refractory Period |
Undershoot is not equal to refractory period length. It plays a role, but they are not equivalents. |
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How does an action potential propagate? |
It spreads the action potential down the axon. As the charge spreads down it causes more action potentials as it goes. Note: charge does go backwards down the axon, but since inactivation gates are closed it does not propagate the action potential this direction. |
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How do ions move down the axon? |
If one ion had to travel all the way down the axon it would be slow, but APs are very fast. To be fast, the ions at the beginning just trigger more ions down the line until the ones at the end of the line are pushed/depolarize to have the desired effect (think golf balls). |
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How do we make action potentials faster? |
Bigger axon diameter (but axons can only get so big) and make length constant longer. |
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Why do we make length constant longer instead of time constant? |
Changing the time constant messes up to o many other things in the cell. |
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How do we make the length constant longer? |
Increase membrane resistance by increasing myelination to prevent leaks. This increases both time and length constant though, so add capacitors in series to decrease capacitance thereby maintaining the same time constant. This can make the time constant 100X longer! |
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Neuregulin |
The signal an axon puts out to say it needs more myelin. No signal = No myelin |
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What is the biggest synapse? |
Neuromuscular Junctions (where neurons synapse onto muscle; huge synapses that you can find when you dissect out muscle. This is how to find synapses!) |
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Different Ways to Explore Synapses |
Can use a pipette to squirt chemicals onto muscle to see reaction. Can use recording electrodes or stimulating electrodes to record or depolarize the cell respectively (intracellular micro-electrode). |
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What is tricky about sticking electrodes into muscle and how do we solve this problem? |
If the muscle contracts, it will break the electrode. If we block the voltage gated Sodium channels then you can prevent contraction while still measuring graded potentials. |
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Acetylcholine Discovery |
Were messing with choline, got acetylcholine and noticed that it changes heart rate in animals, found acetylcholine naturally occurring in mushrooms. Conclude acetylcholine is both bioactive and naturally occurring. When used it lets you replicate simulation of presynaptic neurons. |
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Iontophoresis |
When you add positive charge to an electrode it pushes out a very precise amount of fluid (in this case acetylcholine). It is like a more precise version of pipetting. |
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Finding Acetylcholine's Effects in the Body/Use |
1. Depolarize the axon; Acetylcholine has the same effect as depolarizing the axon (result is an endplate potential). 2. Depolarize the axon with TTX (sodium channel blocker) and there is no endplate potential; Apply acetylcholine with TTX and endplate potential still occurs. Result: Acetylcholine replicates endplate potentials caused by axon depolarization, which is why the endplate potential can still occur when Sodium channels are blocked. |
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Endplate Potential |
Endplate is the muscle, so an endplate potential is just an action potential in the muscle. |
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The Discovery of Discrete Packets of Neurotransmitter |
In common muscle just sitting we occasionally notice mini endplate potentials occurring randomly only in enervated muscle. They observed that these mini endplate potentials were all very similar in size and shape. Hypothesis: acetylcholine was randomly being released. However, it is randomly being released in packets with the same amount of the chemical each time. They found that this is exactly what happens: thus the discovery of synaptic vesicles. |
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How do you make mini endplate potentials occur? |
Put axons in low Calcium buffer. This prevents major endplate potentials, but encourages many mini endplate potentials. They noticed that there was always the same amount or twice or occasionally 3 times that amount. This showed them that there must be some quantum of acetylcholine. Normally many of these are released, but in the mini endplate potentials only 1-3 are released. Result: Quantal Theory of Neurotransmitter Release. This lead to hypothesis for synaptic vesicles. |
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How to Find Synaptic Vesicles |
You can see them under an electron microscope. They observed that all the tiny membrane bound structures were the same size, so that must be what a quantum is. However, they still had to prove these vesicles would fuse to the membrane. This cannot be seen under an electron microscope! |
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Active Zone |
Part of the presynaptic structure where the vesicles are docked. It is right next to the membrane and is where they wait for AP to send the vesicles out. |
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PSD |
Post Synaptic Density - a postsynaptic electron/protein dense area. |
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Quantal Yield |
Different synapses release different numbers of vesicles. Example: neuromuscular junction synapses have huge quantal yields. Different kinds of neurons can also have different vesicle sizes. Vesicle size often depends on the neurotransmitter type. |
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How do we capture vesicle fusion? |
Freeze Microscopy Drop the sample, it hits a switch to trigger an action potential, it lands in a freezing chemical quickly enough that vesicle fusion is still occurring, so the sample is frozen and the fusion is captured. |
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Synapse Overview |
In cell = vesicles. Arrows pointing in = voltage gated calcium channels allow calcium to come into the active zone where it binds with docked vesicles triggering fusion and release of NT. Last step is to get rid of NT in the synapse and reset the active zone. |
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Synaptic Vesicles |
Really small. About 6000 lipid molecules make each one up. It is absolutely covered in proteins. Think of it like a machine! Packed with neurotransmitters. |
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Where do Synaptic Vesicles load? |
They load locally to allow for more flexibility and so you don't have to wait for axonal transport (which would be slow) from the ER. |
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How do Synaptic Vesicles load? |
An anti porter and hydrogen gradient are used to pull neurotransmitter into vesicle. V-ATPase builds up the hydrogen gradient. |
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Calcium Sensor on Synaptic Vesicles |
SynaptoTAGmin - TAP like you're it cause when Calcium taps it, bow it is fusions turns. This sensor is the trigger that holds everything apart until it gets tagged. |
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What happens when synaptotagmin is knocked out? |
The action potential process doesn't work anymore, so we know it must be important. |
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What happens when synaptotagmin is mutated to be less sensitive? |
There is less endplate potential in regular amounts of calcium, but endplate potential reaches normal levels in high levels of calcium. This shows that it is sensing the calcium and that this is what is causing the endplate potentials. |
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In the snare complex, are there any proteins you could knock out and still get a postsynaptic potential? |
Could knock out the SM protein and you would just have random postsynaptic fusion. It would be slower at first because it would be hard for the snares to find each other, but without the SM protein once the snares did find each other they would be constantly randomly fusing causing faster release. |
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Cell Adhesion Molecules |
Cadherins - keep membranes close together. Neuroligin and neurexin - make sure pre and post zones align. |
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RIM Proteins |
Scaffolding that brings calcium channels towards snares. |
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Botox |
A protease that cleaves snare proteins. |
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Botox Results |
Lack of muscle contractions. Cleaved snare proteins ruins motor junction synapses. A lack of muscle contractions causes no wrinkles. No snares also means no fusion; vesicle fusion is disrupted. |
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Do you recover from Botox? How? |
Yes. You have to wait for v and t snares to be made in the cell body and sent down slow axonal transport. Also, by the time the snares arrive at the axon the Botox needs to have been cleared out or decompose or else they will cut up the new snares and the process will have to repeat. Botox is good at sticking around though. That is why it is used. |
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Readily Releasable Pool |
Vesicles primed, docked, and ready to go. Very well organized in lines (we can use freeze fracture microscopy to see them). |
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What if your readily releasable pool it not big enough? |
Ribbon synapses all ready vesicles to attach to it and they stack upwards. This allows for the creation of big big pools. |
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Sequence of NT Release |
1. Action potential 2. Presynaptic terminal depolarization 3. Voltage gated Calcium channels open 4. Calcium enters terminal 5. Vesicle fuses with plasma membrane 6. Neurotransmitters diffuse |
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Calcium Entry into the Presynaptic Terminal (3) |
Voltage Clamp Depolarize to -25 Depolarize to +50 |
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Calcium Entry into the Presynaptic Terminal - Voltage Clamp |
Sodium and potassium channels are blocked, so any current must be from Calcium. |
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Calcium Entry into the Presynaptic Terminal - Depolarize to -25 |
Response is an inward current of Calcium. It takes time to open and just a second to close when the current is turned off. In the postsynaptic cell we see the equivalent of an endplate potential (another inward current). |
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Calcium Entry into the Presynaptic Terminal - Depolarize to +50 |
This depolarization puts us near the Calcium equilibrium potential. This means that there is no driving force for Calcium, so there is no movement or current. However, when we start to depolarize the cell there is a moment before the channels close where there is a driving force, which causes a brief inward current. |
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Calcium & the Time Window |
Adding calcium to cause an endplate potential only works in a very narrow time window. If there is no calcium in the area and you add calcium it only makes the synapse functional if you add the Calcium at the exact right moment where depolarization is happening in the terminal. |
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Fura2 Calcium Imaging |
Shows the calcium imaging. You can see when AP comes through pre-firing of Calcium stream. |
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Caged Calcium |
Triggering intracellular calcium with caged calcium can elicit neurotransmitter response. Cage calcium to give it no effect in the cell. Under a light the calcium becomes uncaged and can have an effect. This reproduces fusion and causes NT release. |
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Vesicle Fusion Observations |
Timing is important (for voltage gated calcium channel opening and vesicle fusion and end plate potential triggering; both occur in less than 2 ms). Therefore vesicles need to be docked near or on target membrane and primed to fuse with membrane quickly (all slow ATP dependent processes have to have already happened). |
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What makes up the snare complex (4)? |
Vesicular snare, target membrane snares, adaptor proteins, and calcium sensor. |
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Vesicular Snare |
Proteins that pull two membranes together; synaptobrevin. |
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Target Membrane Snares |
The two kinds of snares get brought together and wrap up causing the vesicle to be pulled into the target membrane; syntaxin and SNAP25. |
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Adaptor Proteins
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aka SM Proteins; Get the v snares and t snares to associate; Munc18 |
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Calcium Sensor |
Because the whole process is calcium dependent; Synaptotagmin |
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Patch Clamp |
Controls or clamps voltage across membrane to whatever the experimenter chooses so conductance can be studied in isolation. Allows you to study current in single or multiple ion channels. |
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TTX |
Blocks voltage gated sodium channels and silences neuronal firing. |
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TEA |
Similar to TTX, but blocks potassium channels. |
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Specifics of the Patch Clamp Workings |
Patch pipette seals onto surface of ion channel and forms a high resistance seal. It measures voltage. It injects current into feedback circuit so that the pipette voltage matches the command voltage. The amount of current needed to keep the two voltages equal is what is recorded. This allows you to see ion flow. |
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Patch Clamp Student Video Take Homes |
1. Patchclamp recording began in the late 1970’sand is also reffered to as cell-attached patch. This technique uses a patchpipette (electrode) into a plasma membrane of a cell and the high resistancecreated is measured in ohms. This prevents ion flow between a pipette andmembrane. 2. The clamp corresponds to the extracellularpotential of a small patch underneath isolation. For example, TTX was found inbacteria of pufferfish and showed how voltage gated Sodium channels areblocked. The importance of a patch pipette is the voltage and current injectedthrough feedback and the response during a depolarization step. 3. The experiments show how not all channels openimmediately after membrane potential occurs and the driving force getsinfluenced by the different ionic components in the cell. |
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Are neurotransmitters inhibitory or excitatory? |
Neither. The receptor and the context for the NT is what determines whether or not the NT is inhibitory or excitatory. |
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Why vesicles? |
Why not just NT channels? |
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2 Types of Receptors |
Ionotropic and Metabotropic |
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Ionotropic Receptors |
Ligand gated ion channels. Fast! |
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Metabotropic Receptors
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GPCR, G-proteins, secondary messengers. No direct change in membrane potential. Slow. |
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Are ionotropic receptors excitatory or inhibitory? |
Both. |
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Are metabotropic receptors excitatory or inhibitory? |
Both. |
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How do we investigate currents of NT? |
Voltage clamp muscles. |
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Why do we care about currents? |
Helps us figure out what ions are used/there. |
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Two ways to use Voltage Clamp |
1. Set command voltage to elicit currents 2. Use presynaptic stimulation to observe currents |
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Muscle Voltage Clamp Set Up |
Left: current injection and measurement. Center: axon Right: voltage clamp amp; inject current |
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Stimulating 6 Different Voltage Commands |
Depending on what the membrane potential is at when you fire it determines how much depolar/hyperpolarization there will be. |
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Resulting Graph from 6 Different Voltage Commands |
X-axis: command voltage Y-axis: resulting peak current Crosses at 0 - this is the reversal potential. No ion has this as its equilibrium potential, so it must be a nonselective channel. |
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Why do channels sometimes have outward currents and sometimes have inward currents? |
At the reversal potential the current reverses from inward to outward. |
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No current until threshold is reached. Current maximizes after threshold, but when driving force is still high (~ -20 mv). Reversal potential occurs at Sodium's equilibrium potential (~60mv). After this you get an outward current. This graph also allows you to know it is a gated ion channel because it does nothing until threshold. Because the reversal potential is at 60 mV. |
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What is happening? |
Acetylcholine is released. Nonselective ion channels open. Driving force is highest for sodium, so sodium enters. Some depolarization occurs. If things were different, Potassium could leave just as easily. This means it could also be inhibitory. |
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Structure of Ligand-Gated Ion Channels |
5 subunits. Each subunit has many transmembrane amines. Ligand binding site. Some gates that can swing open to let ions in. |
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How did we figure out the structure of Ligand-Gated Ion Channels?
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Blow darts with Curare. Paralyzed animals. This toxin blocked acetylcholine receptors. Examining this in frog eggs let them examine different potential candidates for this channel: over express candidates in the egg. Add acetylcholine to cause inward current. Add curare and inward current in inhibited. This let them find the channels. |
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EPSP |
Excitatory Postsynaptic Potentials |
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IPSP |
Inhibitory Postsynaptic Potentials |
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Difference Between Current and Potential |
Current on top and Potential on bottom. |
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Inhibitory Receptors are often... |
Chloride channels! |
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Why are inhibitory receptors often chloride channels? |
Open chloride channels, membrane potential relatively high, pull membrane potent down to chloride equilibrium potential (-65). Near chloride membrane potential you can get depolarization (different voltages have different effects; CONTEXT MATTERS). However, even if the equilibrium potential is even a little above the membrane potential it is usually inhibitory because opening the chloride channels help to hold the membrane potential at the chloride equilibrium potential making it harder for an EPSP to raise the membrane potential. |
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Active Parts of Neurons |
Voltage gated channels and NT receptors |
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Passive Parts of Neurons |
Myelin sheath, membrane resistance, length and time constants |
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Depending on where the firing occurs defines how much effect it will have. End of dendrites = 20% of total effect Middle = 50% of total effect |
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Dendrite Spines body vs. neck |
Narrow neck isolate the spine body from rest of dendrite so that it can have its own charge. |
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Factors for Strength (4) |
# of postsynaptic receptors: more = stronger
Ca+ concentration Receptor Affinity # of Presynaptic Vesicles Released |
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Spatial Integration
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When you have two synapses that both fire at the same time, so graded potentials run down the cell body at the same time they spatially integrate resulting in a change of both of their mV levels added together. |
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Temporal Integration |
When one graded potential is running down the cell body and another one comes shortly after or at the same time just from a further distance so the first graded potential has its effect and the second one builds on it, but not quite to the level of the two added together. |
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How do you decide if two graded potentials are close enough for temporal integration to occur? |
Look at the time constant. |
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Synaptic Vesicle Recycling |
Production and transportation of NT is energy expensive, so we need a mechanism to recycle these NT so we can have rapid fire APs. |
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2 Kinds of Vesicle Release |
Kiss and Run - not fully fused, partial NT release, vesicle reforms and refills. Full fusion - fully fused, all NT released, proteins reused, synaptic vesicle retrieved back to presynaptic terminal via Clathrin-Mediated Endocytosis. |
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How is excess NT taken up? |
Via plasma membrane symporters (with Na) on presynaptic or glial plasma membranes. |
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How are vesicles refilled? |
VATPase establishes proton gradient in vesicle. Antiporter puts NT in and takes H out. |
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Synaptic Vesicle Recycling Article Takeaway |
Synaptic vesicle retrieval is critical to continuous synaptic transmission. In flies there was a high temp mutation that caused paralysis because vesicles could not be recycled because of a dynemin mutation. |
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Scaffolding Proteins in the Presynaptic Density |
Actin binds to CamK2 which binds to PSD-95 which holds neuroligands and key receptors in place. Neuroligands and neurexin bind to each other. Cadherins bind to each other. |
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How did researchers discover functions of PSD-95 and other receptors? |
Antibody affinity purification: isolate protein antigens of interest, but into column with suspected antibodies, and if you get a match not much will come out of column. |
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Membrane Potential |
Caused by ion differences and selective permeability. |
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What are most neuron's membrane potentials set by? |
Permeability of Cl- and K+ |
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Graded Potentials spread... |
along the membrane over time & space. |
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When do action potentials arise? |
After supra-threshold depolarization, which opens voltage gated sodium channels. |
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When do voltage gated channels close? |
Voltage gated sodium channels quickly close and inactivate while voltage gated potassium channels open. |
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Describe the Driving Forces throughout an Action Potential |
At resting potential, the driving force for Sodium is very high, but after action potential depolarizes the cell the driving force for Potassium is very high. |
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What does an Action Potential result from? |
AP results from changing membrane potential to sodium's equilibrium potential then to potassium's equilibrium potential. |
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When does the refractory period end? |
When the voltage gated sodium channels are able to open again (are no longer inactivated). |
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What is the return to resting membrane potential due to? |
It is due to the current spread within the axon as determined by the time constant (with channels closed). |
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What sets the time of integration as well as the attenuation of more distal synaptic inputs? |
Cable properties. |
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What increases the size and speed of the PSP and where is it located? |
Active properties in the dendrites. |
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What does backpropagation do? |
It can allow for stronger integration for specifically timed inputs. |
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Describe synapse and spines strength relationship. |
Each synapse can encode a particular strength, especially in a spine which has an isolated microenvironment. |
