Local voltage clamping and organotypic cultures of nervous tissue were used to study the actions of a series of agents whose activity is associated with the functioning of the GABAergic and NOergic systems on slow sodium channels. GABA was found not to affect NaV1.8 channel activity, in contrast to substance RGPU-260, a composition of L-arginine and mefebut (β-phenyl-γ-aminobutyric acid methyl ester). Synthetic substance RGPU-260, like its component mefebut, was shown by our data to be able to reduce the functional activity of NaV1.8 channels, giving its use potential as a peripherally acting analgesic drug. Sodium nitroprusside also decreased the functional activity of these channels, though this effect was seen only at relatively high concentrations, while its simultaneous use with RGPU-260 did not lead to any increase in the action on slow sodium channels. Analysis of the resulting data suggested that NaV1.8 channels located in the asynaptic membranes of primary sensory neurons are not controlled by the GABAergic or NOergic systems of the brain.
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Translated from Sensornye Sistemy, Vol. 34, No. 4, pp. 299–306, October–December, 2020.
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Plakhova, V.B., Penniyaynen, V.A., Terekhin, S.G. et al. The Role of Slow Sodium Channels in GABAergic and NOergic Modulation of Nociceptive Neuron Excitability. Neurosci Behav Physi 51, 831–836 (2021). https://doi.org/10.1007/s11055-021-01140-z
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DOI: https://doi.org/10.1007/s11055-021-01140-z