C. Ion channels in pain pathways Flashcards
What voltage-gated sodium channels are expressed in nociceptors that are tetrodotoxin sensitive ?
Nav1.1
Nav1.3
Nav1.6
Nav1.7
what voltage gated sodium channels are expressed in nociceptors that are terodotoxin insensitive ?
Nav1.8
Nav1.9
Nav1.5 which is expressed in the heart
True/false? Voltage-gated sodium channels generate action potentials ?
True
Where are Nav1.7 expressed ?
Nociceptors
Synaptic ganglion neurons
Terigeminal
Olfactory sensory neurons
True or false ? Nav1.7 act as threshold channels which fire action potentials by picking up small depolarisation?
True
Where is Nav1.8 expressed?
DRG and Trigeminal ganglia
When are Nav1.8 activated ?
They are activated at more depolarised membrane potentials than Nav1.7
What would happen if Nav1.8 was removed from a human or mouse ?
Inflammatory pain and cold pain transmission would not be registered as well as neuropathic pain
Where are Nav1.9 expressed ?
DRG sensory neurons and trigeminal ganglian
What are Nab1.9 responsible for ?
Controlling the resting membrane potential thereby regulating neuronal excitability
Describe the structure of voltage gated sodium channel ?
Helix 1-4: Voltage sensing domain
Helix5 and 6: pore forming domain
Loop between 5 and 6: Selectivity filter (sodium sensitivity)
Loop between DII and DIV: inactive loop
What are the different ways in which inhibits can interact with voltage gated sodium channels ?
- Block the closed state
- Inhibit the open state or inactivated state
What are the ways in which sodium channels can be classified ?
- Their selectivity for individual sodium channel isotypes
- Based on the state of the channel they target
- Can be classed based on the combination of the two
What are the types of sodium channel blockers (non-selective)?
LA
Anti-convulsives
Class I antidysrhythmic drugs
What groups do local anaesthetics consists of ?
Hydrophobic part
Ester
Basic side chain (but not all)
Most are tertiary amines
pKa value of 7-9
At pH 7 is a LA ionised or unionised if its pKa is 9?
What would happen if the pKa is 7?
Mainly ionised
7:7 half ionised and half unionised
At pH 9 is a LA ionised or unionised if its pKa is 9?
What would happen if the pKa is 7?
9:9 Half ionised and half unionised
mainly unionised
True or false ?
Non-ionised LA can penetrate the cell membrane and ionised form cannot.
True
What other sodium channel blockers are used to manage pain other than LA?
Carbamazpine
Phenytoin
Lidocaine (although it is a LA)
What does N-type calcium channels (Cav2.2) regulate ?
What are the stages in how they work ?
Regulates transmitter release at nociceptor terminal
- N-type inhibition
- Reduced calcium entry
- Reduced transmitter release
- Analgesia
Name some calcium channel blockers. Do they block the calcium channels ?
Gabapentin
Pregabalin
They do not block the channel pore, they bind to alpha 2 gamma subunit
What type of pain does gabapentin and pregabalin treat ?
Neuropathic pain
What receptors in the nociceptor does capsasin activate ?
TRPV1
