Reply from Damien Samways

Damien Samways — Tue, 11 Mar 2008 14:04:08 -0000

“Is it because of the difference in localization between the TRPV1 and Na+ channels…”

That’s a good question, and it’s possibly a contributing factor. I’m perhaps inclined to say that the main source of the delay is that water-soluble QX-314 diffuses through the extracellar milieu slower than lidocaine (the latter of which can pass through both lipid and aqueous barriers relatively easily). I’m not familiar with the precise nature of TRPV1 localisation in sensory neurons, but it is clearly present in the soma, and one would obviously expect it to be present on the dendritic extremities at least. QX-314 entering at these points would arguably be sufficient to block action potential propagation without diffusing through the whole cell and along the axon.

Another factor factor is QX-314’s permeation through TRPV1. A bulky molecule like that will likely have a very low permeability and low conductance through the open channel and thus probably take a while to accumulate in the cytosol.

Reply from Noah Gray

Noah Gray — Tue, 26 Feb 2008 22:58:40 -0000

This is a great technique and quite clever.

Regarding your therapeutic angle, what is the reason why this methodtakes 30 minutes to take effect? Is it because of the difference in localization between the TRPV1 and Na+ channels, and therefore diffusion of QX-314 is required before pain sensitivity is reduced?

Recent replies to "JOURNAL CLUB: Special Delivery of Anesthetics"

Reply from Damien Samways

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