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
