Lecture 4: Ion Channels and Transporters

Question 1

What are the 4 properties ion channels and the currents flowing through them should have?

Answer 1

1. Large ion currents indicate that the channels have to be capable of allowing ions to move across the membranes at high rates.
2. Channels have to make use of the electrochemical gradients of various ions.
3. There are channels selective only for Na+ or only K+.
4. Because the conductances are voltage-dependent, channels have to be able to sense changes in membrane potential

Question 2

What does the patch clamp method measure?

Answer 2

the current flowing through a single ion channel

Question 3

What are the 4 different configurations of the patch clamp method?

Answer 3

1.Cell-attached recording.
2. Whole-cell recording.
3. Inside-out recording.
4. Outside-out recording.

Question 4

Describe cell-attached recording

Answer 4

there’s tight contact between the recording electrode/pipette and the membrane, the electrode is small enough to record from a single ion channel

Question 5

Describe whole-cell recording

Answer 5

creates a tight seal between the pipette and membrane, then with a strong pulse of suction it creates a small break in the suction which makes the cytoplasm continuous with the pipette, now you can measure the current in the cell and can add anything intracellularly via the electrode

Question 6

Describe inside-out recording

Answer 6

electrode attaches to a small region of the membrane and creates a break where you separate the membrane from the channels and now the cytoplasmic domain is accessible

Question 7

Describe outside-out recording

Answer 7

use the electrode, and pull it out which creates a break at 2 points where the ends of the membrane anneal and makes the extracellular domain accessible

Question 8

What is the probability of sodium channels opening w.r.t. to membrane potential?

Answer 8

The probability increases as you increase depolarization

Question 9

What is the probability of potassium channels opening w.r.t. membrane potential?

Answer 9

The probability increases as you increase depolarization

Question 10

true of false: channels for both sodium and potassium are voltage-gated

Answer 10

true

Question 11

true or false: sodium and potassium channels open at the same time during depolarization

Answer 11

false

Question 12

true or false: sodium and potassium channels close during hyperpolarization

Answer 12

true

Question 13

What do sodium and potassium channels have that detect the potential across the membrane?

Answer 13

a voltage sensor

Question 14

What channel opens first?

Answer 14

sodium

Question 15

What channels open second?

Answer 15

potassium

Question 16

What inactivates sodium channels?

Answer 16

depolarization but it leads to a nonconducting state, indicating an additional mechanism for inactivation

Question 17

Describe the functional states of voltage-gated sodium and potassium channels

Answer 17

Initially, when the membrane depolarized, sodium channels go from the closed state to an open state and sodium can enter the neuron, potassium channels remain closed and as time goes on the sodium channels get inactivated and potassium channels open so potassium can flow out of the cell
When MP is brought back to rest, both channels close

Question 18

What happens to a neuron treated with alpha scorpion toxin?

Answer 18

increases sodium current leading to the prolonged current of an action potential

Question 19

What happens to a neuron treated with beta scorpion toxin?

Answer 19

changes the activation of sodium channels to a more hyperpolarized potential so sodium channels can be activated at higher hyperpolarized potentials than they could, and it shifts the conductance curve of sodium to the left

Question 20

What are the 4 types of ion channels?

Answer 20

1. Voltage-gated ion channels:
   - Na+ channels.
   - K+ channels.
   - Ca2+ channels.
   - Cl- channels.
2. Ligand-gated ion channels:
   - Neurotransmitter-gated.
   Cyclic nucleotide-gated.
3. Transient receptor potential family.
   - Thermosensitive channel.
4. Mechanosensitive channel.

Question 21

Describe voltage-gated calcium channels

Answer 21

Start at rest, hold membrane potential at a higher potential and leads to calcium current

Question 22

Describe neurotransmitter-gated channel

Answer 22

AMPA receptors bind the excitatory neurotransmitter, glutamate, a neurotransmitter binds to the channel, they open and current can flow through the channel, activate synapses by binding to glutamate, get excitatory postsynaptic current

Question 23

Describe cyclic nt-gated channel

Answer 23

the cyclic nts are acting on channels on the intracellular side, activated by light

Question 24

Describe thermosensitive channels

Answer 24

open in response to temperature change, different temperatures activate - some open in response to higher or lower temperatures

Question 25

Describe mechanosensitive channels

Answer 25

Open in response to mechanical stimuli, get a displacement, which leads to current flowing through the channels

Question 26

How do ions permeate through channels?

Answer 26

via ion-selective pores

Question 27

Describe the ion channel pore

Answer 27

The pore is composed of the arrangement of loops and helices of the subunits that make up the channel.
The pore is large enough for only the ion for which it is meant to pass through and therefore, makes the membrane permeable to that ion.

Question 28

What is the selectivity filter?

Answer 28

Each ion channel has a specific selectivity filter that ushers in a particular ion, while excluding others, including those of the same valence

Question 29

What organism was early work on ion channel pores done on?

Answer 29

bacteria potassium channels

Question 30

What makes up the ion channel pore?

Answer 30

The transmembrane domains with a selectivity filter and the inner/outer helices

Question 31

Why are molecular specializations important?

Answer 31

They permit gating of ion channels by different types of stimuli

Question 32

Why are voltage-gated channels larger than other types of channels?

Answer 32

Each channel subunit has additional transmembrane structures that form the voltage sensors for that channel

Question 33

What do voltage sensors contain?

Answer 33

positively charged amino acids

Question 34

How do voltage sensors move?

Answer 34

depolarizations push the senors outward and hyperpolarizations pull the sensors inward then sensors pull on the helical linker connecting the sensors to the pore then pull it open or push it closed

Question 35

Describe the structure of mammalian voltage-gated potassium channels

Answer 35

when the membrane is hyperpolarized, gets deconfiguration (channel closed)
when the membrane depolarized, leads to a conformational change that opens the pore, so voltage sensors detect changes in membrane potential and change conformation allowing the channel to open – other voltage-gated channels operate in a similar manner

Question 36

What are some neurological diseases caused by altered ion channels?

Answer 36

Epilepsy
Ataxia
Migraine headaches
Pain
Deafness
Blindness

Question 37

Describe how altered ion channels can cause pain

Answer 37

a mutation known as IEM (inherited erythromelalgia) in sodium channels affects sodium channel function, sodium current is larger and lasts longer in IEM, associated with burning pain and if you measured action potentials between wildtype and neurons with this mutation, higher frequency of AP in this mutation, get an increase in sodium current and it stays activated longer so greater amplitude and results in increased AP frequency

Question 38

Describe how altered ion channels can cause deafness

Answer 38

a mutation known as SANDD (sinoatrial node dysfunction and deficit) is found in a gene for calcium channels, when you depolarize the neuron, the mutation prevents calcium current, and the affected calcium channel is specifically involved in hearing, so this mutation causes a loss of hearing