Voltage Gated Ion Channels

From the amino terminus to the carboxy terminus, describe the structure of the membrane spanning domains of voltage gated K channels.

- amino terminus consists of the inactivation ball on the cytoplasmic side - between the inactivation ball domain is the T or tetramerization unit - there are 6 membrane spanning domains - domain 4 is the voltage sensor with basic + charges imparted by lots of lysine and arginine residues - the pore is between the 5th and 6th membrane spanning domain - the carboxy terminus is on the cytoplasmic side

From the amino terminus to the carboxy terminus, describe the voltage gated Na+ channel.

-amino terminus is on the cytoplasmic side. No inactivation ball. (instead an inactivation gate later -6 membrane spanning domains repeat 4 times along the cell membrane -an inactivation gate is between the 3rd and 4th subunits -the carboxy terminus is on the cytoplasmic side. *the Na+ channel is like 4 K+ channels put together.

What two things does reversal potential depend on?

1) the selectivity of the channel 2) the concentration of permeant ions

You're testing the current flowing through a voltage-gated channel over a range of known voltages. As you increase the voltage, you see the current flow: A. become more positive B. become more negative C. stay the stame

A. Become more positive. The more positive (higher) the test potential is (voltage is potential) --- the more positive the current is.

The nicotinic receptor channel is a nonselective channel that leads to a depolarization of the cell when a ligand binds. This receptor channel therefore must: a) have a reversal potential that is more negative than that of a potassium channel b) have a reversal potential that is more positive than the membrane threshold c) have a reversal potential that is more negative than the membrane threshold but more positive than the potassium channel reversal potential

B) have a reversal potential that is more positive than the membrane threshold. This channel, when open, will try to pull the cell's voltage towards its resting potential voltage. For it to do so and cause depolarizations, it therefore must have a reversal potential that is higher than the membrane threshold. With A, a hyperpolarization would occur. With C, a passive response would occur.

A channel has a reversal potential of -65 mV. The cell has a current membrane voltage of -40 mV. If that channel opens, what will happen? a) inward current will occur and the voltage of the cell will move toward the reversal potential b) outward current will occur and the voltage of the cell will move toward the reversal potential c) the channel will not stay open because the voltage difference is too great d) the channel will adapt to the current membrane voltage

B) outward current will occur and the voltage of the cell will move toward the reversal potential. -channels will try to pull the cell's voltage to meet their reversal potential. -use channels' reversal potential to predict movement of current. -outward current: makes the cell more negative--- like the undershoot of K+ channels during the refractory period which pull the cell voltage to be more negative. Therefore to go from -40 mV to -65 mV, you need an outward current to become more negative like the reversal potential of the channel.

Deleting the amino terminus of the voltage gated K+ channel results in a loss of which state of K+ channel activity? a) open b) closed c) inactive

C) inactive. The amino terminus holds the "ball" of the ball and chain model of inactivation of K+ channels.

True/False: Drugs like Bupivacaine and Prenylamine are effective at blocking potassium channels, thereby dampening inward current and demonstrate what is called use-dependent block where the binding affinity of the drug increases as more drug binds (additive effect).

False! That statement was true except for the word potassium. Use-dependent block is seen with bupivacaine and to a larger degree with prenylamine on SODIUM channels, dampening the inward current. These drugs are used in conditions with too much pulsation (epilepsy, arrhythmia).

True/False: Use-dependent block of Na- channels with bupivacaine and prenylamine is irreversible.

False. Eventually the drug will "fall off" the channel and the effect will wear off.

True/False: Permeation and gating qualities of a voltage-gated channel are regulated by the same molecular domains but act independently of one another.

False. They act independently of one another AND are regulated by different molecular domains.

True/False: Voltage-gated ion channels let many types of ions through their pore, dependent on the valence of the ion.

False. Voltage-gated ion channels are highly selective to one ion alone.

Because of how fast ions move through pores when their gates are open, researchers determined these pores are filled with ______.

H20

How does reversal potential (E rev) differ from Nernst potential (E ion) ?

Nernst potential for an ion is the voltage at which a particular ion will cease its flux through that ion's channels and current is zero. Nernst potentials are idealized for perfectly selective channels. Reversal potential is like the Nernst potential--- only with the more realistic observation that not every channel is perfectly selective.

Imagine a graph of current vs. voltage with current on the Y axis and voltage on the X axis. You plot the observed current for given voltages through a voltage gated channel. What does the point where the line crosses the X axis signify?

The X intercept is the reversal potential. It is the point where current is zero, and marks the shift between inward and outward current.

Define reversal potential

The membrane voltage at which the net current through a channel is zero. If the membrane potential (V) does not equal Erev, the net current will flow to bring the membrane potential towards Erev.

What class is the VR-1 receptor channel part of and how is it stimulated?

This is the stretch/heat-activated class of ion channels in neurons. Also called transient receptor potential (TRP). It responds to environmental cues such as H+, heat, and ligands like capsaicin (chili peppers) NONSELECTIVE-- lets Ca+ or Na+ through

True/false: The voltage sensing units of the voltage sensitive potassium channel are in close contact with the other transmembrane units of the channel pore, so as these voltage sensing units move where charges are, they physically pull on the other central units and open or close the pore.

True.

True/False: for a positive Inward current is negative by convention and outward current is positive by convention.

True. The super screwed up part is that inward current, which is called negative current, is a description for sodium, and sodium movement into the cell makes the membrane potential more positive. Outward current, called positive current, is a description for potassium, and potassium movement into the cell makes the membrane potential more negative. I hate physicists.

Voltage gated K+ channels are (monomeric/dimeric/trimeric/tetrameric) and have (4/5/6/7/8) membrane spanning domains

Voltage gated K channels are tetrameric and have 6 membrane spanning domains.

How do voltage changes affect the likelihood that a voltage gated channel will be open?

Voltage gated channels only have a likelihood to be open within a small window of voltage range. There's a steep sloping off between the probability of a channel being open and a change in voltage.

What are three examples of ligand gated channels and how do they work?

When a ligand binds, they open and ions move down their concentration gradient. 1) Neurotransmitter receptor (Glutamate for example binds and triggers opening of channel so Na+ can flow into cell, K+ out of cell) -- can be NONSELECTIVE- lets Na+ or K flow through or SELECTIVE (example of Cl- selective glycine receptor) 2) Ca+ activated K+ channel (Intracellular Ca+ binds to the cytoplasmic side of the channel, triggering opening and K+ movement out of the cell) 3) cAMP gated channel- (cAMP binds the cytoplasmic side of the channel, triggering opening and movement of Na+ inside the cell and K+ outside the cell) NONSELECTIVE- lets Na+ or K flow through

Describe how the pore domain of the potassium channel effectively excludes Na+ even though it's moving ions at a rate of 6,000,000 per second?

You'd think it's via sidechains of amino acids, because there's a characteristic Glycine-Tyrosine-Glycine pattern along the pore in every K+ channel. But it's NOT these amino acids that have a filtering effect. K+ moves through its own channel pore without a problem (as fast as if it were water itself through a pore) because its size allows the positively charged cation to interact favorably with the negative dipole moment of oxygen groups sticking out into the pore. Na+ is smaller and can't interact favorably with those groups, so it can't move through effectively.