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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

References:

  • Plakhova V.B., Penniyaynen V.A., Rogachevsky I.V., Kalinina A.D., Podzorova S.A., Krylov B.V. Roly donora molekul NO v regulycii otvetov pervichnogo sensornogo neirona [Role of the donor of no molecules in regulation of primary sensory neuron responses]. Sensorniye sistemy [Sensory system]. 2019. V. 33 (2). P. 135–141 (in Russian). https://doi.org/10.1134/S0235009219020069
  • Tyurenkov I.N., Bagmetova V.V., Borodkina L.E., Berestovitskaya V.M., Vasil’eva O.S. Fenibut i ego citrate v preduprezdenii psichonevrologicheskich naruschenii, vuzvannuch chronicheskim stressom – lischeniem paradoksalynoi fazu sna [Fenibut and its citrate prevent psychoneurological disorders caused by chronic stress paradoxical sleep deprivation]. Experimentalinay i klinicheskay farmakologiy [Russian Journal of Experimental and Clinical Pharmacology]. 2012. V. 7 (6). P. 8–13 (in Russian).
  • Akopian A.N., Sivilotti L., Wood J.N. A tetrodotoxin-resistant voltage-gated sodium channel expressed by sensory neurons. Nature. 1996. V. 379. № 6562. P. 257–262
  • Desvignes C., Robert F., Vachette C., Chouvet G., Cespuglio R., Renaud B., Lambas-Senas L. Monitoring nitric oxide (NO) in rat locus coeruleus: differential effects of NO synthase inhibitors. Neuroreport. 1998. V. 8. № 6. P. 1321–1325. https://doi.org/10.1097/00001756-199704140-00001
  • Elliott A.A., Elliott J.R. Characterization of TTX-sensitive and TTX-resistant sodium currents in small cells from adult rat dorsal root ganglia. J. Physiol. (Lond). 1993. V. 463. № 4. P. 39–56.
  • Gold M.S., Reichling D.B., Shuster M.J., Levine J.D. Hyperalgesic agents increase a tetrodotoxin-resistant Na+ current in nociceptors. Proc. Natl. Acad. Sci. USA. 1996. V. 93. № 3. P. 1108–1112.
  • Hamill O.P., Marty A., Neher E., Sakmann B., Sigworth F. Improved patch-clamp techniques for high-resolution current recording from cells and cell-free membrane patches. Pflügers Arch. 1981. V. 391. № 1. P. 85–100.
  • Kostyuk P. G., Krishtal O. A., Pidoplichko V. I. Effect of internal fluoride and phosphate on membrane currents during intracellular dialysis of nerve cells. Nature. 1975. V. 257. № 5528. P. 691–693.
  • Kostyuk P.G., Veselovsky N.S., Tsyndrenko A.Y. Ionic currents in the somatic membrane of rat dorsal root gangli on neurons – I. Sodium currents. Neuroscience. 1981. V. 6. № 12. P. 2423–2430.
  • Krylov B.V., Rogachevskii I.V., Shelykh T.N., Plakhova V.B. Frontiers in pain science. Volume 1. New nonopioid analgesics: understanding molecular mechanisms on the basis of patch-clamp and quantumchemical studies. Sharjah, U.A.E., Bentham Science Publishers Ltd., 2017. 203 p.
  • Lai J., Porreca F., Hunter J.C., Gold M.S. Voltage-gated sodium channels and hyperalgesia. Ann. Rev. Pharmacol. Toxicol. 2004. V. 44. P. 371–397. https://doi.org/10.1146/annurev.pharmtox.44.101802.121627
  • Lapin I. History of drug development. Phenibut (β-PhenylGABA): a tranquilizer and nootropic drug. CNS Drug Reviews. 2001. V. 7. № 4. P. 471–481. https://doi.org/10.1111/j.1527-3458.2001.tb00211.x
  • Lopatina E.V., Yachnev I.L., Penniyaynen V.A., Plakhova V.B., Podzorova S.A., Shelykh T.N, Rogachevsky I.V., Butkevich I.P., Mikhailenko V.A., Kipenko A.V., Krylov B.V. Modulation of signal-transducing function of neuronal membrane Na+,K+-ATPase by endogenous ouabain and low-power infrared radiation leads to pain relief. Med. Chem. 2012. V. 8. № 1. P. 33–39. https://doi.org/10.2174/157340612799278531
  • Millan M.J. Descending control of pain. Prog. Neurobiol. 2002. V. 66. № 6. P. 355–474. https://doi.org/10.1016/s0301-0082(02)00009-6
  • Penniyaynen V.A., Plakhova V.B., Rogachevsky I.V., Terekhin S.G., Podzorova S.A., Krylov B.V. Molecular mechanisms and signaling by comenic acid in nociceptive neurons influence the pathophysiology of neuropathic pain. Pathophysiology. 2019. V. 26. № 3–4. P. 245–252. https://doi.org/10.1016/j.pathophys.2019.06.003
  • Plakhova V., Penniyaynen V., Yachnev I., Rogachevskii I., Podzorova S., Krylov B. Src kinase controls signaling pathways in sensory neuron triggered by low-power infrared radiation. Can. J. Physiol. Pharmacol. 2019. V. 97. № 5. P. 400–406. https://doi.org/10.1139/cjpp-2018-0602
  • Tyurenkov I., Perfilova V., Vasil’eva O., Rogachevskii I., Penniyaynen V., Shelykh T., Podzorova S., Krylov B., Plakhova V. GABA- and NO-ergic modulators control antinociceptive responses. Act. Nerv. Super. Rediviva. 2018. V. 60. № 1. P. 1–8.
  • Vaiva G., Thomas P., Ducrocq F. Low posttrauma GABA plasma levels as a predictive factor in the development of acute posttraumatic stress disorder. Biol. Psychiatry. 2004. V. 55. № 3. P. 250–254. https://doi.org/10.1016/j.biopsych.2003.08.009