Ion channels

Question 1

Define ionotropic

Answer 1

Receptor which is pore-forming. In contrast to metabotropic, which are indirectly linked to channels.

Question 2

What dictates the direction of flow of ionotropic receptors?

Answer 2

Electrochemical gradient

Question 3

How are ligand gated channels classified? Give examples.

Answer 3

By size. Trimer eg P2X; tetramer eg NMDA, AMPA, Kainate; pentamer eg nicotinic Ach, 5-HT, GABA, Glycine

Question 4

Give examples of some voltage gated ion channels

Answer 4

Calcium channels
Sodium channels
Potassium channels

Question 5

Give some CVS drugs targeted at calcium channel

Answer 5

Dihydropyridines target vasculature & cause relaxation. Eg AmloDIPINE
Non-dihydropyridines; Phenylalkylamines target the heart & cause relaxation. Eg Verapamil
Benzothiazepines have intermediate sensitivity. Eg Diltiazem

Question 6

Give some non-cardiac drugs targeted at calcium channels

Answer 6

Chronic pain: N-type CCs in the dorsal horn for morphine-unresponsive patients. Eg Ziconotide
Epilepsy: Alpha 2 delta subunit targeted by Gabapentin and pregabalin to modulate calcium influx at synapses. Also for chronic pain and depression.

Question 7

Give some examples of sodium channel drug targets

Answer 7

Anaesthesia: procaine and lidocaine create a use-dependent block. 
Arrhythmia; in the blood, acts as a class I antidysrythmic
Epilepsy; phenytoin and carbamazepine

Question 8

Give some examples of potassium channel drug targets

Answer 8

Epilepsy; Ezogabine opens channels to reduce exitability

BUT Kv11.1 blockade induces LQTS and will result in torsades des pointes