Equilibrium Potentials + Ion channels Flashcards
T/F
The resting potential of a cell is negative because there is more Na+ outside the
cell than inside the cell, and Na+ is a positive ion.
False
- There are equal #’s of negative ions, the inside of the cell is electrically neutral
- Concentration of Sodium outside the cell remains the same, and its tiny fluxes of ions across the membrane that creates this potential difference
- The charge of the cell is not changed the difference is found right at the membrane
The number of ions needed to create the electrical potential is…
- very small!
-> (For K+ = 10-12 moles of K+ per cm2 of membrane)
Why is the resting membrane potential negative if there’s more K+ inside the cell?
Isn’t K+ a positive ion?
- More Cl-, and K+ would flow out if the K+ is open
The concentration of ions on each side remains essentially …
constant
Tiny fluxes of ions do not disrupt …
- chemical electroneutrality
- (Each ion has an oppositely charged counter-ion, such as chloride)
- The intracellular and extracellular fluids are electrically neutral
Cell membrane:
- Lipid molecules arranged in a bilayer.
1) Polar, hydrophilic heads face outwards.
2) Hydrophobic tails extend into the middle.
3) Proteins are embedded in the bilayer and make
contact with both the extracellular fluid and the
cytoplasm.
4) Can be defined in terms of their ion selectivity and the factors that control their opening and closing
General characteristics of ion channels:
- Ion channels contain:
1) Aqueous pore
2) Selectivity filter
3) Gate
Aqueous pore:
- allows substances such as ions which are soluble in water to pass into the cell.
Selectivity filter:
- restricts ion permeability based on size and ionic charge.
Gate:
- Most channels are gated. They fluctuate between open and closed states. At rest, K+ channels are open. They determine the resting membrane potential. At rest, the remainder of channels are predominantly closed.
Channels can also be “gated”:
- they switch between being open and closed
Three different models for channel gating:
- 1: A discrete conformational change occurs in one region of the channel
- 2: A general conformational change occurs along the length of the channel
- 3: A blocking particle swings in and out of the channel mouth
Channel gating is controlled by several types of stimuli
- 1: Binding of a chemical to the channel (ligand-gated channels)
- 2: Phosphorylation of the channel
- 3: Changes in membrane voltage (voltage-gated channels)
- stretch or pressure of the channel
Structure of the K+ channel pore and selectivity filter:
K+ channel:
- details of a bacteria
- Subunits that each cross the membrane twice.
- “pore-loop”
Channels may enter a — or inactive state in which they are closed and incapable of being opened.
- “refractory”
- The inactive state can be relieved only when the membrane returns
to its original resting membrane potential
Four subunits together form the…
- complete K+ channel
- selective filter
- Outer helix
- Inner helix
- Pore helix
Structure of the pore:
- it is well suited for conducting K+ ions.
Selectivity filter:
- The narrowest part is near the outside mouth of the channel.
Only “nonhydrated” K+ ions can enter
Start of the K+ channel
K+ moving through the K+ channel selectivity filter
- Draws in Positively charged ions
- With these aminos:
- Aspartic acid, glutamic acid (- charge)
The water-filled cavity at the center of the channel
- Allow K+ to interact with water molecules (for stabilization)
- With the following:
- Threonine, Isoleucine, Phenylalanine
Dehydration of K+
- Glycine pulls H+ atoms from water molecules
- It’s at either end, so it allows K+ to move through either end of the channel.
Why can Na+ not go through K+ channel
- It is attracting Na+ ions, but the precise diameter of this channel means that K+ ions (dehydrated) can be stabilized in the watr configuration. A Na+ atom and its associated water molecules would be smaller and so the glycine would not be able remove the water, thus the Na+ is not sufficiently dehydrated and the size of the channel is precise.
The opening and closing of this K+ channel is not dependent…
- on the voltage difference across the membrane (membrane potential).
- But other K+ channels are voltage-dependent
Voltage-gated channels have …
- sensors that detect the electrical potential across the membrane.
Example: positively charged alpha-helices
In the mammalian K+ channel, the voltage-sensor for a K+ channel:
- S4 = voltage sensor
- S3b-S4 = paddle (+ charge)
- S5-S6 = pore
When the membrane is depolarized, the paddle-like sensor…
- moves towards the extracellular surface, opening the pore.
- at rest, the membrane is - charged and the paddles are pulled down to a close
There are nearly a hundred
kinds of potassium channels.
How they differ + Their function
- They differ in their gating
properties: how they open and
close. - Their most important function:
maintaining the membrane
resting potential!
The Na+ channel has 4 subunits.
- Each subunit contains an alpha helix S4 which functions as a voltage sensor
-> sensitive to changes in membrane potential - There is a pore loop between S5 and S6
Na+ Channel
- Selectivity filter
- Voltage Sensor
- Gate
Properties of the voltage-gated Na+ channel
- They open with little delay
- They stay open for about 1 ms.
- They quickly inactivate.
- They can’t be opened again until the membrane returns to near-threshold.
The Na+ channel twists open when the membrane depolarizes
- The channel has alpha-helix domains which are positively charged.
- When the membrane potential changes, the shape of the channel changes. This allows the pore to open.
- The closed pore is pulled down towards the floor of the cell
Note how the channel is closed when the membrane potential is -65mV
States of the Na+ channel
- Closed: no ions can pass through
- Open: when the membrane becomes depolarized, the channel opens and Na+ ions can enter the cell
- Inactive: as the membrane remains depolarized, the pore of the channel becomes blocked. No Na+ ions can enter
- Closed: When the membrane returns to rest, the block is removed and the channel becomes closed.
Diversity of ion channels:
Channel gating is controlled by several types of stimuli
1: Binding of a chemical to the channel
2: Phosphorylation of the channel
3: Changes in membrane voltage
4: Stretch or pressure of the channel
How can we study the activity of
individual channels?
-The patch-clamp technique
- Whole-cell: recordings from the entire cell.
- Inside-out: record from a single channel. Can look at how chemicals affect the cytoplasmic side of the channel.
- Outside-out: record from a single channel. Can look at how chemicals affect the extracellular side of the channel.
Advantages of the patch-clamp technique:
1) Can observe activity of only a few channels
rather than the thousands in an entire cell.
2) Can observe very small amounts of current.
3) Can examine the effects of adding ions or
chemicals to either the internal or external
environment.
Patch-Clamp
Voltage and Current
- Voltage: the experimenter controls this
- Current: the amount of current flowing
through the channel
The probability of a Na+ channel opening depends on…
membrane potential
