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The role of slow sodium channels in GABA and NO-ergic modulation of the excitability of a nociceptive neuron

© 2020 V. B. Plakhova, V. A. Penniyaynen, S. G. Terekhin, S. A. Podzorova, A. D. Kalinina, B. V. Krylov

Pavlov Institute of Physiology of Russian Academy of Sciences 199034 St. Petersburg, Makarova emb., 6, Russia

Received 23 Jun 2019

The effects on slow sodium channels of a number of agents, the activity of which is associated with the functioning of GABA- and NO-ergic systems, was studied by patch clamp and organotypic nerve cell culture methods. It was found that GABA does not affect the activity of NaV1.8 channels, in contrast to RGPU-260, which is a composition of L-arginine and mefebut (methyl ester of beta-phenyl-gamma-aminobutyric acid). According to our data, the synthetic drug RGPU-260, as well as its component mefebut, is able to reduce the functional activity of NaV1.8 channels, which makes their use promising as an analgesic drug with a peripheral mechanism of action. It was found that sodium nitroprusside also reduces the functional activity of the studied channels, but this effect is observed at relatively high concentrations, and its combined use with RGPU-260 does not enhance the effect on slow sodium channels. Data analysis shows that NaV1.8 channels located in the asynaptic membrane of the primary sensory neuron are not controlled by GABA and NO-ergic brain systems.

Key words: nociception, sensory neurons, patch-clamp method, organotypic nerve culture method, NaV1.8 channels, GABA, RGPU-260, mefebut, sodium nitroprusside

DOI: 10.31857/S023500922004006X

Cite: Plakhova V. B., Penniyaynen V. A., Terekhin S. G., Podzorova S. A., Kalinina A. D., Krylov B. V. Rol medlennykh natrievykh kanalov v gamk- i no-ergicheskoi modulyatsii vozbudimosti notsitseptivnogo neirona [The role of slow sodium channels in gaba and no-ergic modulation of the excitability of a nociceptive neuron]. Sensornye sistemy [Sensory systems]. 2020. V. 34(4). P. 299–306 (in Russian). doi: 10.31857/S023500922004006X


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