Neuronal Na+ channels

Cummins At least from my evidence concerning closed state inactivation of Na channels (Cummins et al 1998), it might be that the inactivation is dependent on the channels opening for the peripheral neuronal channels, as opposed to skeletal muscle channels, which are more likely to inactivate from the closed states. This may be why you see such a concordance between the Hinf (steady-state inactivation curve) and the voltage-dependence of the persistent current the peripheral neuronal Na channels may have to open if they are going to inactivate. 

Bean It is unclear how general such direct effects of acetazolamide are. Donella Green came over to our lab and we did some experiments together on Na channels in neurons, and didn t see significant blocking activity. It may be unclear whether in her experiments on skeletal muscle channels it was a direct effect on the channels or something less direct on the cells. It looked unhkely to her and me that there was a direct effect on neuronal Na" channels. 

Inactivation of LA clinical effect occurs by diffusion away from the neuronal Na+ channels and by uptake into the vas nervorum and into the systemic circulation. It is here that metabolic inactivation of the linkage between the aromatic ring and tertiary amine can occur. The mechanism and site are very different for the amide and ester local anesthetics. 

Barbier, J., Lamfhanh, H., Le GaD, F., Favreau, P., Benoit, E., Chen, H GiDes, N., Ilan, N., Heinemann, S,H Gordon, D Menez, A., and Molgo, J. (2004) A6-conotoxin from Conus ermineus venom inhibits inactivation in vertebrate neuronal Na channels but not in skeletal and cardiac musdes./. Biol. Chem., 279, 4680-4685. 

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