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Neuroscience Test 1 - Ion Channels

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What does it mean that ion channels can only be opened and closed in response to certain stimuli?
They are gated!
What are the two types of gated channels?
1. Voltage gated
2. Ligand gated
What are the four ways to classify ion channels by activator?
1. External ligand gated
2. Internal ligand gated
3. Transmembrane voltage gated
4. Pressure or temperature gated
In most channels, can ions move in both directions or not?
Both directions
What are the family of channels that have four subunits called?
The S4 family
Name three channels that are S4 channels.
K, Ca and Na
The S4 family has how many transmembrane domains in one subunit?
Six in one subunit
What is the purpose of using the patch clamp technique?
It allows one to look at the individual channels in isolation
What is single channel conductance?
When one channel opens, it always allows a certain amount of ion current through. This is the single channel conductance.
How do you calculate the single channel conductance?
Current divided by driving force
What is the sum of the time a channel is open divided by total time?
Open probability
Which channels initiate and propagate action potentials?
Na channels
Sodium influx causes...
Depolarization
How do you re-activate an inactivated sodium channel?
Hyperpolarize the cell
What causes sodium channels to open?
Depolarization
With a typical voltage clamp, what type of data do you collect? Macroscopic or microscopic?
Macroscopic
Which subunit in a sodium channel has the actual pore forming units?
The alpha channel
What are the auxillary subunits in the sodium channel for?
Modulation of the channel
Are Na channels very conserved genetically?
Yes
How many AA is the alpha subunit in a sodium channel? kDs?
About 2000 aa and 250 kD
How many homologus domains do you have in a sodium channel? How many TM segments? Are they hydrophobic or hydrophilic?
1. 4 homologous domains
2. 6 TM segments
3. Hydrophobic
Between which two segments do you find the P Loop?
5 and 6
What is the name for the segment that helps form the channel?
The P Loop
The P Loop is (not conserved/conserved) in all sodium channels.
Conserved
S4 contains (positively/negatively) charged AAs.
Positively
Which segments are considered the voltage sensor segments?
1-4
What happens to S4 when you depolarize the cell?
It turns, opening the channel silly!
The intracellular domain that acts as an inactivation gate in sodium channels is between...
Domain 3 and domain 4
The critical residues needed to block the sodium channels are (hydrophobic/hydrophilic).
Hydrophobic
Does inactivation of a sodium channel involve S4?
Absolutely not, geez.
How many homologous domains are there in a calcium channel?
4
Which segment of a calcium channel is charged?
S4
What do you use to differentiate between different calcium channels? You do the same for sodium channels.
The P Loop
Does the S3-S4 loop play any role in calcium channels?
Not really
True or false: Calcium has many roles.
True
Which has more auxillary subunits, calcium or sodium?
Calcium
Basically, what is the role of auxillary subunits in calcium channels?
To regulate how fast or how slow the channel opens. It provides more of a regulatory role.
What are the three types of high voltage calcium channels?
1. L Type - muscle
2. N Type
3. P/Q - synapse
What is the main type of low voltage calcium channel?
T Type
How many genes encode each of the types of calcium channels?
1. L Type - 4
2. P/Q Type - 1
3. N Type - 1
4. T Type - 3
What is the potassium channel's role?
Repolarization
True or false: There are some K channels with 6 TM regions and some with 2.
True
What type of channel was the first to be cloned? What was it called?
K channel; shaker
How is a K channel different than a Na channel in composition.
A K channel is a tetramer while a Na channel is a monomer
What mediates the inactivation of a K channel?
The n-terminus. It is like a ball and chain.
How does a calcium-dependent K channel work?
You need calcium present to be able to conduct potassium.
What are the two types of CDKC?
1. SK - only Ca dependent
2. BK - can be voltage or Ca dependent
Which has a larger conductance BK or SK?
BK bitch!
Which families do the BK and SK channels belong to?
Both the 7TM and 6 TM family.
How do you activate the BK?
There is a RCK loop on the c-terminus that supposedly may involve calcium binding to control the gate.
What is constitutively bound to SK channels?
Calmodulin
In order to have an action potential, a certain number of what kind of channels must open?
Na Channels
What two types of channels mediate action potentials?
1. Na
2. K
Which type of channel in an action potential is slightly delayed in its opening?
K channels
Information sent through neurons is encoded by the (blank) of the action potentials.
Frequency
How will a stronger stimulus affect the action potential?
It will cause an increase in frequency.
Why would you not be able to stimulate an AP if you were to stimulate the nueron very slowly?
You end up inactivating all your sodium channels before you can produce an action potential.
What two factors are encoded into the frequency of an action potential?
Intensity and rate.
Does the diversity in firing patterns come from the sodium channel?
No the sodium channel is generally preserved. It has to do with the diversity of the other kinds of channels.
Can differences in the types of potassium channels affect the frequency of firing?
Yes, there is a large diversity in the types of K channels accounting for a lot of the variety in firing frequency.
Which K channel is known as the transient k channel?
Ia - activates faster and inactivates
Which K channel is known as the delayed rectifier?
Ic or Idr - this one takes longer to activate and inactivate
With hyperpolarization will there be more or less channels inactivated in general?
Less
With more depolarization, will there be more or less channels inactivated in general?
More
How does one re-activate an inactivated sodium channel?
Hyperpolarize the cell
Why do you get faster, shorter action potentials with Ia channels?
Because the channel activates and inactivates faster allowing the channel to repolarize faster. This allows you to reset the Na channels for a new AP!
When using a Ia channel, what is the real limitation of the firing of the next AP?
The refractory period
What will the action potential with a Ic channel look like? Why?
It will be wider because the channel is slower to activate which means the neuron is slower to repolarize. This means you have to wait longer to start the next AP.
Why is there a delay in firing when a cell is hyperpolarized?
Because the cell is hyperpolarized, there are less inactivated Ia channels. So when the neuron is stimulated both Ia and Na channels open. The Ia channels dominate the Na channels. This means it takes longer to get to threshold for an AP to occur.
Why is there not a strong response in a cell that is depolarized closer to threshold?
More Na are inactivated because of the level of depolarization. This means there won't be as big of an inward Na current.
Which type of K channel keeps the RMP close to the quilibrium potential of K? Does it inactivate?
Im channel; no
Which channel opens at a lower voltage, Na or T-type Ca?
T-Type Ca
What do the T-type Ca channels help do for the firing of an action potential?
Helps depolarize the cell, opening Na channels
Are both activation and inactivation voltage dependent in T-type Ca channels?
Yurs
What do the L-type Ca channels activate?
The CDKC. Once activated, they will open and let lots of K out of the cell.
Which type of CDCK is used in bursting?
SK Type
What does the current from the CDCK channels contribute to?
Afterhyperpolarization
A greater AHP will (slow/speed up) the firing rate of the neuron. Why?
Slow down because it will make it tougher to get back to the threshold of Na.
What do Ih channels do?
They are triggered by hyperpolarization. Once opened, they allow Na and K to pass with a reversal potentail of about +35mV.
Where do you find Ih channels?
In pacemaker cells like the heart.
Go through a bursting cycle
1. Ih channels open enough to cause a small depolarization which...
2. Opens T-type Ca channels that depolarize the cell more and that...
3. Activated Na channels which depolarize the cell and then...
4. L-type channels open cause Ca to accumulate which...
5. Opens SK CDKC which...
6. Repolarize the cell and cause an AHP
7. Which reactivates the Ih channel

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