ion channel targets - pharmacology

Question 1

which VGSC are insensitive to TTX

Answer 1

5 8 9

Question 2

where are VGSC 1.7 located and what is its key role

Answer 2

expressed in nociceptors as well as ganglion neurons
threshold channel for firing action potentials
upregulated after inflammation
INFLAMMATORY PAIN

Question 3

where are VGSC 1.8 located and what is its key role

Answer 3

sensory specific channel
activate more at depolarised membrane potentials
role in INFLAMMATORY PAIN and COLD PAIN transmission
some role in neuropathic pain

Question 4

where are VGSC 1.9 located and what is its key role

Answer 4

sensory specific
do not contribute to action potential upstroke
help control membrane potential

Question 5

how are VGSCs structured in terms of domains and helicies

Answer 5

six helicies
1-4 voltage sensing domain
5-6 pore forming domain
loop between 5 and 6 selectivity filter
loop between domain 3 and 4 inactivation loop

Question 6

what are the phenomena that contribute to the safe use of VGSC blockers (3)

Answer 6

• use of dependant block
• selectivity for specific channel isotopes
• local application of non specific drugs

Question 7

what are lidocaine, tetracaine and procaine all examples of

Answer 7

local anaesthetics

Question 8

describe the three key chemical aspects of the structure of local anaesthetics

Answer 8

• hydrphobic aromatic region
• ester or aminde linker
• basic amine side chain

Question 9

what do the pka values of local anaesthetics range between

Answer 9

7-9

Question 10

if the pH is 7 and a local anaesthetic is 9, is it ionised or not

Answer 10

ionised

Question 11

how do local anaesthetics work in terms of cellular interactions and binding to the channel

Answer 11

act intracellularly
enter in unionised form across membrane of cell
ionise in cell (gain a hydrogen)
binds to sodium channel intracellularly in ionised form
higher affinity for inactive form of channel

Question 12

how does the sodium channel blocker carbamazapine work

Answer 12

stabalises inactivation of the channel

Question 13

where is the N type Ca2+ (Cav2.2) channel located

Answer 13

synapse in dorsal horn

Question 14

where does gabapentin and pregabalin act

Answer 14

calcium channel blocker
bind to the alpha two delta subunit

Question 15

what does capsaicin do

Answer 15

activates TRPV1 on nociceptor
eventually becomes neurotoxic and TRPV1 receptors lose function