Sodium Channels

PH3113 Unit 1

How many transmembrane domains are in the alpha subunit of a sodium channel?

4

How many segments are in each domain?

6

What is important about the S4 segment?

Acts as a voltage sensor as it contains positive charge (arginine) that moves when voltage changes to open channel

What is the loop called between S5 and S6 and why is it important?

P loop forms a selectivity filter so only lets Na+ through

What is the loop between domain III and IV called and why is it important?

IFM loop acts as an inactivation gate that physically blocks the channel after it opens

Where are voltage gates sodium channels concentrated?

Nodes of ranvier in myelinated neurones

Name a drug that targets sodium voltage ion channels and its MOA.

local anaesthetics such as lidocaine block NaV channels from the inside of the cell, stopping action potentials so there is no pain signal. Outside the cell they are uncharged and lipophilic. Inside the cell, they become charged so they can bind to the channel and block it.

What is use dependant block?

When a drug binds to active cells more when they are open or inactivated. Therefore, the more open channels, the stronger the drug effect.

What drugs work via use dependant block and what is the advantage of this?

Local anaesthetics

Antiepileptic drugs mean that they don’t affect normal neurones and act best when activity is high (during seizure)

What makes up the selectivity filter of NaV channels?

DEKA

D-aspartate

E-Glutamate

K-lysine

A-Alanine