Ion Channel Physiology Lecture Sep 23

Question 1

Why can’t charged molecules passively diffuse through membranes?

Answer 1

Charged molecules - especially ions– cannot cross cel lmembranes because the lipid part of the membrane has high electrical resistance.

Only lipophyllic molecules can passivly diffuse through the membrane

Question 2

What three membrane components provide routes for charged molecules to cross the membrane?

Answer 2

gap junctions

membrane transporters

ion channels

Question 3

How do ion channels and transporters differ? (4 ways)

Answer 3

1. Ion channels are ALWAYS passive. Transporters can be either passive or active (using ATP)
2. Ion channels are essentially holes - there is a direct connection between the extracellular and intracellular fluids. Transports use conformational changes to move molecules from one side to the other - there is never a direct connection between the two sides.
3. Ion channels only move ions. Transports can move ions, but can also move larger molecules such as glucode.
4. Ion channels are very fast (millions/second), whilc transportes tend to be slower (hundreds/second)

Question 4

At a basic and critical level, what must you have in order to have a current across a membrane. i.e. a charge gradient?

Answer 4

transports/ion channels

V = IR

You don’t have flow without channels

Question 5

What happens when red blooc cells are placed in a hypotonic solution? Why?

Answer 5

THey lyse. RBCs have aquaporins so in a hypotonic solution, water wille nter through aquaporins through osmosis.

Question 6

Which direction will ions (or water) flow through chanels?

Answer 6

Trick question! Channels are bidirectional by definition!.

Question 7

Why don’t aquaporins allow ions to cross?

Answer 7

There is an area in the center of the channel with positive residues. This means the water molecule need to rotate appropriately to pass through. This rotational space is the appropriate side for water molecules only, so the aquaporin is selective.

Question 8

What convers selectivity for channels?

Answer 8

The structural filter - an area in the channel that is shaped/charged appropriately for only one molecules (or a couple molecules)

Question 9

What happens when a cell with no aquaporins is put in a hypotonic solution?

Answer 9

No osmosis, no cell lysis (at least not on a short time scale)

Question 10

What are the two fundamental ion characteristics?

Answer 10

They are selective and they are gated.

Question 11

What are the four ways channels can be gated?

Answer 11

Leaky (essentially always open even though they could close- neurons)

mechanically gated (hooked to the cell membrane and if you deform the membrane, the channel will be pulled open - sensory neurons )

ligand gated (ligand binds and conformation changes - NT receptors)

voltage gated (membrane voltage changes and you get channels open - excitable cells)

Question 12

In addition to gating, what are some channels capable of to prevent the flow of ions?

Answer 12

Inactivvation

Question 13

Which of the following is least likely to pass through an individual channel?

1. only Na+
2. Na+ and K+
3. Na+, K+, Ca2+
4. only Cl-
5. Na+ and Cl-

Answer 13

Na+ and Cl- would never cross through the same channel. All the other combos are possible.

Question 14

Which f the following is elast likely to be directly responsible for opening an ion channel?

1. Membrane stretch
2. random changes in the position of the channel gate
3. depolarizaiton of the cell membrane
4. Change in extracellular ion concentration
5. Binding of a drug to the channel

Answer 14

4

The channel itself doesn’t give a shit what the concentration of ions is on either side of the membrane.

Question 15

What is the different between closing and inactivating a channel?

1. The structure of the selectivity filter is altered during inactivation but not when channels close.
2. All gated channels can close; only some channels can inactivate.
3. Ions can flow through inactivated channels, but not through closed channels.
4. Inactivation is random, but specific mechanisms are used to close a channel (mechanical stimulation, change in membrane voltage, binding of a ligand).

Answer 15

2 is the correct answer.

number 4 is close because inactivation IS random, but specific mechanisms are used to OPEN a channel, not CLOSE a channel.

Question 16

Do all living cells have a negative or positive resting potential?

Answer 16

negative

Question 17

What happens in depolarization?

What happens in hyperpolarization?

Answer 17

depolarizaiton: making the membrane more positive
hyperpolarizaiton: making the membrane more negative

Question 18

Why is the membrane potential always fluctuating?

Answer 18

Because there are hundreds of different types of channels with thousands of each type present in the membrane, with some open and some closed.

Question 19

What law defines the relationship among the membrane potential (Vm), current and conductance/resistance?

Answer 19

Ohm’s law:

V = IR or I = CV

Question 20

All live cells have a resting membrane potential that isn egative with respect to the extracellular fluid.

Why do electrically excitable cells have a much larger RMP (-30 to -70 mV)?

Answer 20

They have a larger number of K+ channels open at rest (allowing K+ to flow down the concentration gradient until reaching the equilibrium)

Question 21

What two gradients detemine the direction of ion flow?

Answer 21

Electrochemical gradients are easy.

Concentration gradietns are a little more confusing.

Question 22

What is the ranking of extracellular ion concentrations?

What is the most prevalent ion in the extracellular space? THe intracellular space?

Answer 22

Na+ > Cl- > K+ > Ca2+

Na+ is the most prevalent in the extracellular space

K+ is the most pprevalent in th eintracellular space.

Ca2+ is the lowest in both places.

Question 23

Under normal conditions, which ion is the only ion whose concentration gradient favors movement of the ion from the inside to the outside?

Answer 23

K+ is the only one.

All the others are in higher concentration in the extracellular space, so the concentration gradient favors movement from the outside to the inside.

Question 24

What are the extracellular concentrations of Na+?

How about intracellularly in muscle and neurons?

Answer 24

Extracellular: 135-145 mM

Muscle: 10 mM

Neurons: 5-10 mM

Question 25

What is the extracellular concentration of K+?

In muscle cells? In neurons?

Answer 25

Extracellular: 3.5 -5 mM (narrow window must be TIGHTLY regulated)

Muscle: 155 mM

Neurone: 140 mM

Question 26

What is the extracellular concentration of Ca2+?

How aobut in muscle? In neurons?

Answer 26

Extracellular: 1.2 mM

Muscle: .0001 mM

Neuron: .0001 mM

Question 27

What is the extracellular concentration of Cl-?

In muscle? In neuron?

Answer 27

Extracellular: 95-105 mM

Muscle: 10-20 mM

Neuron: 4-30 mM

Question 28

Under normal conditions, in living cells, do concentration gradients “run down.”

Answer 28

No. Ion channels may use the gradient made by the Na/K ATPase activity, but the concentration gradient isn’t destroyed in the process -it’s constantly being regenerated by the ATPase.

Question 29

What fators determine how much ion you have extracellularly? How about intracellularly?

Answer 29

Extracellularly: diet, kidney function

Intracellularly: what transports you have

Question 30

What is the primary function of neuronal Na+.K+ ATPase? What does it mean to say the ATPase is only mildly electrogenic?

Answer 30

THe primary function is the establishment of the concentration gradients for Na+ and K+

The action of ATPase are only mildly electrogenic, meaning the net result of the actions of the ATPase is a Vm of about -5 to -12 mV, which is a long way aways from the 070 of the resting potential.

What arranges for the higher membrane potential is ion channels that move massive amounts of ion depending on the concentrations of Na+ and K+.

Question 31

What are the two rules of ion movement?

Answer 31

1. movement is bidirectional
2. concentration gradients do NOt change from an ion channel’s point of view. THe direction of flow is determined by the electrochemical gradient and a chemical gradient, which determine direction of flow AND magnitude. They do not always go in the same direction.

Question 32

What is the reversal potential?

How is it calculated?

Answer 32

It’s the membrane potential where the net flow thoruh any open channel is 0.

In other words, at E rev, the chemical and electrical forces are in balance.

It’s calculated using the Nernst equation.

For Na+ is’a about 60 mV and for K+ it’s about -88 mV

Question 33

What equation is used to determine the equilibrium/reversal potential?

Answer 33

The nernest equation:

Here it is modified to reflex 37 degrees C

E rev = (61/Z) x log ( []o / []i )

where z=the charge on the ion

Question 34

What are the equilibirum potentials for Na+ and K+ and Cl-?

Answer 34

Na+ = 60 mV

K+ is -88 mV

Cl- is -61 mV

Question 35

For K+ with a Erev of -88 mV:

In what direction will the net ion flow go at the following membrane potentials and why:

+60 mV

0

• 60
• 88
• 10

Answer 35

At +60 mV, the flow will be out because the chemical gradient is pushing them out (K+ is very high inside), and the electrical gradient is pushing them out (the inside it charged positive)

At Vm= 0 mV, the net flow will still be out because the chemical gradient is still pushing the K+ out (it hasn’t reached its reverse potential yet). The electrical gradient is actually not involved with this one because if there’s no membrane potential, there’s no flow based on electrical gradient - no current.

At Vm = -60 mV, the net flow is still out. The chemical gradient is sitll pushing K+ out. However, the electrical gradient is now pulling K+ in since the inside of the cell is negative now. But in this case, the chenical gradient wins out - we still haven’t reached the reverse potential.

At Vm = -88 mV, no net flow will occur. This is because we have reached the reverse potential and the chemical gradient forcing K+ out is perfectly balanced by the electricalg radient pushin ght eK+ in, so you ge tno flow.

At Vm = -100 Vm, the net flor of K+ will be in. The chemical gradient will still want to push K+ out of the cell, but now that the membrane potential is so low, the electrical gradient wins out and pulls the K+ into the cell.