Ion Channels as Drug Targets

What are the different types of ion channel? Ligand-gated, mechanically gated, leak/passive (always open), and voltage-gated

Ion channel structure = membrane pores made up of protein subunits which allow ions to enter or leave the cell. Excitable cells such as nerve cells, skeletal muscle cells and cardiac cells have many ion channels as they need to respond quickly.

Action potential formation involves voltage gated ion channels:

• Stimulus applied which meets/exceeds threshold → sodium ion channels open and sodium enters the cell increasing charge within the cell

• potassium ion channels open and potassium leaves the cell

• sodium ion channels become refractory so no more sodium enters the cell

• potassium ions continue leaving the cell causing membrane potential to return to resting potential

• potassium outside the cell diffuses away and more potassium diffuses out down the electrochemical gradient

• potassium channels close

transmitter release = action potential relays down the nerve until it reaches the end organ where transmitter release happens

sodium channel blockers = many different classes (weak, moderate and strong) used for different conditions

class IA sodium channel blockers = disopyramide, quinidine, procainamide

class IB sodium channel blockers = lidocaine, tocainide, phenytoin, mexiletine

class IC = flecainide, propafenone

lidocaine mechanism of action = blocks the voltage gated sodium channel from inside the cell. Lidocaine is used for pain relief eg at the dentist

Calcium ion channel action = mediate contraction in the vascular smooth muscle controls blood pressure.

What are calcium ion channel blockers used to treat? cardiac arrythmias, hypertension, angina pectoris and other conditions

angina pectoris = narrowing of coronary arteries