Mechanism of immobility

[Ref: SH4:p35-38]

Immobility is produced by actions of AA on spinal cord, rather than higher centres

Mechanisms

• Depression of excitation
  * e.g. AMPA and NMDA receptor-mediated currents
• Enhancement of inhibition
  * e.g. GABAa and glycine receptor-mediated currents
• Actions of Na+ channel (but not K+ channel)

However,

• Cholinergic receptors do not play a significant role
• Opioid receptors are not involved

NB:

From [SH4:p36]

"Overall, no inhaled anaesthetic action on a single group of receptors can explain immobility, and immobility as a result of concurrent actions on many receptors is unlikely"

--> ???

Inhibitory receptors

Glycine receptors are major mediators of inhibitory neurotransmission in the spinal cord
--> Mediates part of the immobility produced by inhalational AA

GABAa receptors mediate immobility produced by injected AA

GABA and inhalational agent

• GABAa receptors probably do not mediate immobility produced by inhaled AA [SH4:p36]
• But at the same time, maximal enhancement of GABAa receptors also occurs at the partial pressure of AA used in clinical practice. [SH4:p38]

 

Glutamate receptors

• Glutamate is the principle excitatory neurotransmitter in CNS
• Glutamate receptors include G-protein coupled receptors and ligand-gated receptors

Ligand-gated glutamate receptors include:
* NMDA receptors
* AMPA receptors
* kainate receptors

• NMDA receptors are important mediators of immobility produced by inhaled AA
• AMPA mediates the initial (fast) component of excitatory postsynaptic transmission
  --> Likely to be involved in immobility produced by inhaled AA
• Role of kainate recptors on MAC is unclear

NB:

[SH4:p37]

??? Inhaled AA acts on NMDA and AMPA receptors in the spinal cord

??? Inahled AA does not act on the same receptors in the brain

 

Action on sodium channel

Inhaled AA does not inhibit voltage-dependent Na+ channels

Inhaled AA inhibits presynaptic Na+ channel and/or voltage-gated calcium ion channel
--> Inhibition of presynaptic release of neurotransmitter (especially glutamate)

Thus, IV lidocaine decreases MAC