Lecture 5: Ion Channels and Transporters pt.2

Question 1

What are the 2 types of ligand-gated ion channels?

Answer 1

1. neurotransmitter-gated ion channels
2. cyclic nucleotide-gated ion channels

Question 2

How do neurotransmitter-gated ion channels work?

Answer 2

The AMPA receptors have a clam-shell-shaped ligand binding domain, an extracellular ligand like glutamate binds to this domain and causes the clamshell structure to shut, this leads to the gate helices of the transmembrane domain to move, allowing the channel pore to open and the ion moves through

Question 3

What are the 3 domains of the AMPA receptor?

Answer 3

amino-terminal domain, ligand-binding domain, and carboxyl-terminal domain

Question 4

What do AMPA receptor antagonists do?

Answer 4

Block the channels

Question 5

How do cyclic nucleotide-gated ion channels work?

Answer 5

Light triggers a pathway in these neurons that allows intracellular ligands like cyclic GMP to bind to the binding domain, the binding domain undergoes a conformational change that moves the linkers, thereby opening the channel gate and allowing cations to flow through the channel pore

Question 6

What are the 4 subunits of a cyclic nucleotide-gated channel?

Answer 6

1. pore-forming domain
2. voltage sensor domain - sometimes affected
3. linker
4. cyclic-nucleotide binding domain

Question 7

How do temperature-sensitive TRP channels work?

Answer 7

TRPV1 channel is gated by heat or capsaicin, they can open the channel pore by displacing membrane lipids closely associated with the helical linker that connects the sensor-like domains to the pore, causing a conformational change and opens the channel gates

Question 8

What 2 gated channels is the structure of temperature-sensitive TRP channels similar to?

Answer 8

voltage-gated potassium and cyclic nucleotide-gated channels

Question 9

What gated channel is the function of cyclic nucleotide-gate channels similar to?

Answer 9

voltage-gated potassium channel

Question 10

true or false: TRP channels don’t have a selectivity filter and let cations flow through

Answer 10

true

Question 11

How do mechanosensitive gated channels work?

Answer 11

Gated by mechanical displacement, members of the Piezo family are sensitive to touch and are extremely large with 38 transmembrane-spanning helices, they form a pore for cations and form 3 blades that act as levers for sensing membrane curvature, when mechanical force flattens the membrane, it flattens the curvature and this leads to tension building up which pushes the levers and the channel opens

Question 12

What maintains the concentration gradient for all physiologically relevant ions?

Answer 12

active transport

Question 13

What do active transporters require?

Answer 13

energy

Question 14

What does the Na/K ATPase pump do?

Answer 14

maintains the gradient for Na and K

Question 15

What does the Ca ATPase pump do?

Answer 15

prevents the intracellular [Ca] from accumulating

Question 16

What are the 2 types of Ca ATPase pumps?

Answer 16

1. PMCA
2. SERCA

Question 17

What does the PMCA do?

Answer 17

Responsible for extruding calcium from the cell of the neuron - pumps calcium out

Question 18

What does SERCA do?

Answer 18

Responsible for removing calcium from the cytoplasm and pumping it into the sarcoplasmic reticulum

Question 19

How does the Na/K ATPase pump work?

Answer 19

Using the hydrolysis of ATP, ATP binding promotes 3 Na removed and 2 K taken in, where pump phosphorylation promotes extracellular release of sodium and binding of potassium

Question 20

What happened to the efflux of sodium when external potassium was removed?

Answer 20

Reduced efflux of sodium

Question 21

What happened to the efflux of sodium when external potassium was returned?

Answer 21

Recovery of efflux of sodium

Question 22

What happened to the efflux of sodium when ATP inhibitors were applied?

Answer 22

Reducing ATP synthesis has a significant decrease on the efflux of sodium

Question 23

What happens to efflux of sodium when ATP synthesis is restored?

Answer 23

Recovery of sodium efflux

Question 24

What is sodium efflux dependent on?

Answer 24

external potassium and ATP

Question 25

Describe the translocation of Na and K by the Na pump

Answer 25

sodium binds, ATP phosphorylates the pump and leads to a conformation change and the efflux of sodium, allowing potassium to bind then dephosphorylations lead to another change in conformation (slightly different from the first conformational change), and potassium released

Question 26

What do ion exchangers do?

Answer 26

Carry one or more ions up their electrochemical gradient, while simultaneously taking another ion down its gradient

Question 27

What do ion exchangers use for energy?

Answer 27

Use the electrochemical gradient of other ions

Question 28

What are the 2 types of ion exchangers?

Answer 28

1. antiporters
2. co-transporters

Question 29

What are 2 examples of antiporters?

Answer 29

1. Na/Ca exchanger
2. Na/H exchanger

Question 30

What do antiporters do?

Answer 30

exchange intracellular and extracellular ions

Question 31

What does the Na/Ca exchanger help do?

Answer 31

keep intracellular [Ca] low

Question 32

What does the Na/H exchanger help do?

Answer 32

regulates intracellular pH

Question 33

What are 3 examples of a co-transporter?

Answer 33

1. Na/K/Cl co-transporter
2. K/Cl co-transporter
3. Na/neurotransmitter co-transporter

Question 34

What do co-transporters do?

Answer 34

carry multiple ions in the same direction

Question 35

What does the Na/K/Cl co-transporter help do?

Answer 35

regulates intracellular [Cl]

Question 36

Which ion’s gradient do antiporters use to function?

Answer 36

sodium

Question 37

Describe the function of the Na/Ca exchanger

Answer 37

binding of cytoplasmic Ca causes the gating bundle to slide across the core helices, changing the conformation to face outward, then the outward-facing conformation releases Ca outside the cell, next the inward-facing conformation releases Na into the cytoplasm and the outward-facing conformation binds Na, causing the gating bundle to slide back to restore the inward-facing conformation