Kv Channels

Front 1

What is the relationship between voltage, current, and resistance (you're screwed if you don't know this)

Back 1

V=IR

Front 2

What is the Nernst equation?

Back 2

E=(RT/zF)ln([S]out/[S]in): (RT/zF) equals around 58 if at room temperature and ion is monovalent

Front 3

Why is the Nernst potential never exactly as the equation predicts?

Back 3

Because ion channels aren't ever perfectly selectively permeable to only one ion and membranes are rarely completely impermeable either

Front 4

What is the normal resting potential of most neurons? SA node?

Back 4

-70mV; -30mV (point is, the range is large, don't really need to memorize this)

Front 5

What ions are primarily extracellular? Intracellular?

Back 5

NaCl is extracellular. K+ and organic anions is intracellular

Front 6

The IV curve of a certain channel population has its x intercept at 0. What does this mean?

Back 6

This means that there is either no concentration gradient for the conducted ion(s) or the channel is non-selective

Front 7

T or F, without ionic ATPases like the Na+/K+ the reversal potential for most ions would be around 0

Back 7

True, you need the ATPases to establish concentration gradient

Front 8

Biophysically, what causes channel rectification?

Back 8

A concentration gradient so intense that the anomalous ion effect occurs or the structure (affinity/binding pockets) of the channel are asymmetric.

Front 9

T or F; potassium channels tend to be slow and non-inactivating

Back 9

False, potassium channels are a really diverse family and there exists really fast channels in the muscle and slower channels in the heart

Front 10

T or F; knowledge of a channel's activation kinetics will also allow you to determine the inactivation kinetics

Back 10

False, some channels don't even have inactivation. Since physically different parts of the protein are ALWAYS incharge of activation and inactivation they are kinetically independent

Front 11

I discovered a new channel that conducts blorg. I want to know if the channel homoligermerizes. Luckily, fleeb drug inhibits the blorg channel. What experiments can I conduct to determine homo-oligomerization?

Back 11

I can see the stoichiometry of the inhibitory effect. If there is a plateauing at a certain ratio then blorg channel may oligomerize at this ratio. Once I have a hypothesized oligomerization stoichiometry, I can then create fusion proteins of multiple blorg channel proteins in a row and do mutation studies (to determine if each position contributes to the channel equally).

Front 12

What is the Kv channel selectivity sequence? Why is this sequence good?

Back 12

TIGYG, it's good because all of these residues are rather hydrophobic. Remember that potassium is conducted in a dehydrated state.

Front 13

Describe the knock-on model for Kv channels

Back 13

Basically, the Kv channel has 4 binding sites, but only 2 K+ ions will ever occupy these sites. Since they repel each other, the ions will always occupy either site 1 and 3 or 2 and 4. Only when a new K+ ion is dehydrated and pushed into the channel will one of the ions be "knocked" out on the other side. Without the other ion the two would just jump between position 1 and 3, and 2 and 4. It is thought that a single water molecule is between the two K+ ions.

Front 14

Describe how K+ ions are coordinated by water then by AAs of the Kv channel

Back 14

A single K+ is coordinated by 8 water molecules then by the C=O AA bonds of the selectivity filter.

Front 15

Like sodium channels, potassium channels are gated via the bottom (intracellular) portion of S6. However, there exists two main mechanisms by which this gating occurs in potassium channels. Describe these differences and the advantages conferred by both

Back 15

If it's a pretty stiff alpha helix, it will close in a sort of cone type way. This is useful because the gate becomes "tighter" allowing it to be blocked by small molecules and other ions. If there is a floppy glycine or PXP motif in the helix it will hinge and fold over the pore to close it. This allows larger gating proteins to interact and close the channel

Front 16

T or F, every positive residue in S4 contributes equally to gating

Back 16

False, they may move the S4 segment equally, but some interact more with key AA residues in other parts of the protein that are more important in channel gating.

Front 17

You find a drug that can bind irreversibly to positively charged AAs. You can now happily find out how much S4 sticks out when hyperpolarized. How?

Back 17

Basically, if your drug binds to an exposed positive AA in the S4 it won't go back in, meaning depol won't open your channel. Therefore, you selectively KO positive AA one by one from S4 until you the channel still activates even when drug exposed

Front 18

When recording gating current from opening potassium channel, we see a range where 4-8 charges will move per gating event. Why the range?

Back 18

Because not every single S4 will move during depol

Front 19

Describe the gating mechanism of Kv in as much detail as you can

Back 19

During depol, the movement of S4 will move the S4-S5 linker into a position where it can interact with S6. This interaction will open the channel.

Front 20

Why is the Phe233 important for S4 in Kv

Back 20

This is a hydrophobic plug that keeps the S4 domain from moving too far.

Front 21

What is the Cole-Moore shift phenomenon? Why is this phenomenon important?

Back 21

Basically, the current increase over time is less sigmoidal if the cell was more hyperpolarized (greater single channel opening delay). Don't need to know the details of this, but it basically showed that the old subunit-active-or-not-active model wasn't enough (introduction of preopened state)