L9 Ion channel function

What are these structure made of:

Primary structure

Secondary structure

Tertiary structure

Quaternary structure

Primary structure -sequence of amino acids

Secondary structure -alpha helix

Tertiary structure -3D folding of polypeptide

Quaternary structure-different polypeptides bonded together

Describe the structure of a voltage-gated Na⁺ channel.

4 domains, each with 6 transmembrane α-helices; one helix forms the pore and another (S4) acts as the voltage sensor.

How does the s4 alpha helix act as a voltage sensor

- Has lots of positive charge

- When the inside of the cell is negative, the S4 is attracted inward towards the cytosol

- When the inside of the cell is positive the S4 is repelled to the extracellular space

- This movement is what opens and closes the channel in response to membrane potential changes

What do the S5 and 6 alpha helix pores do in the voltage gated sodium channel

- They allow sodium to pass

- Pore loop between them contributes to the selectivity filter making the channel sodium specific

- Inner parts are hydrophilic to allow water and ions through, surrounding ares arehydrophobic to anchor in at the membrane

Which of the alpha helicies of the voltage gated sodium channels are hydrphic and which are hydrophilic and how does this affect their structure

S1,2 and 4 are hydrophobic and bind to the cell membrane

S2 is hydrophilic and gets pushed to the center forming a water soluble through which water can bind to and pass through

What are heterooligomers and homooligomers

Distinct subunits

Single subunits

What determines ion channel selectivity

Size of the pore and electrical charges of chains of amino acids that enter the pore

Explain the potassium selectivity filter

- Filter is perfectly sized to replace K+ hydration shell with carbonyl oxygen from the channels

- K+ fits snug so energetic cost of removing water is compensated

- Na+ is smaller so if it enter without water it cannot make full contact with both sides of the filter (too short to bond properly) but if it keeps extra water molcules it would be too big therefore it cannot go through the potassium channel

Explain the sodium selectivity filter (add diagram)

- Ions in solutions are surrounded by a hydration shell (water molecules bound by electrostatic attraction)

- To pass through the channel, they must shed their waters of hydrogen but only if the channel can replace those interactions (with amino acids mimicking the hydration shell via hydrogen bonding or electrostatic interactions)

- Sodium channel filter perfectly sized to coordinate sodium without water, replacing hydration with polar amino acids

- Potassium is too large: if it tries to enter with water its too big and if it sheds its water then the channel cannot fully replace the hydration bonds because the potassium doesnt fit tightly enough on both sides so the energetic cost is too high

What is the patch clamp technique?

Used to measure tiny current through a single ion channel (in picoamps)

It does so by isolating a small path of cell membrane with a glass micropipette

List 3 types of ion channel gating mechanisms and what they require to be opened/closed

Ligand- need binding of a chemical eg a transmitter

Voltage- need a voltage change across the membrane

Mechanically - need stretching or some displacement

What is an agonist

It's a ligand that binds to a receptor and activates it or opens the channel. It can be a neurotransmitter or hormone and usually binds to the extracellular side of a channel

What is an Antagonist and give the 3 examples (CLT)

It inhibits binding of endogenous ligand

- Curare: blocks nicotinic ACh receptor

- Lidocaine: local anesthetic, binds to domain 4 of sodium channel preventing AP generation

- Tetrodotoxin (TTX): binds to voltage gated sodium channels preventing AP generation

What is an indirect gated channel (add diagram)

A channel opened by an intracellular second messenger activated by a neurotransmitter.

What are the 3 states of the sodium channels (add diagrams)

State what they are and what happens with the activation and inactivation gate and why that happens

1. resting- closed and activatable so activation gate is closed, and inactivation gate is open. Got positive charge on it in S4 which is attracted to the negative inside the cell

2. Activated- open so activate gate is open and inactivation gate is open. Confirmation change occurred causing activation gate to open. Inactivation gate is open as inside of the cell is positive which replls the positive inactivation gate

3. Inactivated- closed and non-activatable where the activation gate is open and the inactivation gate is closed

How do the activation and inactivation gate operate

Activation: opens due to confirmational change which occurs in regions of the channels

Inactivation: Blocking particle swings into an out of channel mouth

How are mechanically-gated channels activated? (add diagram)

By stretch or pressure — mechanical forces deform the membrane or cytoskeleton. eg inner ear hair cells

Describe nicotinic receptors in skeletal muscle.

Type of ion channels, how many subunits and isforms, selective for what and what is the binding process

- Ligand gated: opened by ACh from nerve

- 5 subunits for the channel pore

- 2 isoforms of subunit N1(on the skeleton) and N2 (on the nerve)

- Selective for cations eg Na+, K+

- motor neuron AP travels doen axon released ACh into the synaptic cleft

- ACh binds nicotine receptor on membrane channels (N-cholinergic) which opens and Na+ goes in

- Depolarization of musce cell triggers muscle AP and movement occurs

Describe voltage-gated sodium (Nav) channels.

found where, type of ion channels, how many subunits and what does it do

- Nav found in nerves

- Voltage gated- opened by depolarization

- Single alpha subunits forms the pore

- Complete channel has an accessory beta subunit

- 9 alpha subunits (Nav 1.1-1.9) and 3 beta subunits (beta 1-3) so there can be 27 different channels

- Opening depolarizes nerve causing AP