• 2024 (Vol.38)
  • 1990 (Vol.4)
  • 1989 (Vol.3)
  • 1988 (Vol.2)
  • 1987 (Vol.1)

Investigation of Src-kinase inhibitor PP2 effects on modulation of slow sodium channels by ouabain

© 2017 Т. N. Shelykh, I. V. Rogachevsky, V. N. Moshkina, S. A. Podzorova, B. V. Krylov, V. B. Plakhova

Pavlov Institute of Physiology, RAS, 199034 Saint-Petersburg, Makarova emb., 6.

Received 03 Aug 2016

Possible involvement of Src-kinase in transduction of nociceptive signals evoked by binding of ouabain to the transducing site of Na+, К+-АТPase was investigated by patch-clamp method. Speci c Src-kinase inhibitor (PP2) introduced into intracellular solution prior to extracellular action of ouabain at low concentrations was demonstrated to totally block modulation of slow sodium channels NaV1.8 by ouabain: the value of effective charge transfer (Ze ) of Nav1.8 channels activation gating device after ouabain application was the same as in the control experiments. Src-kinase was thus shown to be involved as a series unit in transduction of the nociceptive signal from Na+, К+-АТPase to NaV1.8 channel.

Key words: nociception, patch-clamp method, slow sodium channels, cardiotonic steroids, Src-kinase, Na+, К+-ATPase

Cite: Shelykh Т. N., Rogachevsky I. V., Moshkina V. N., Podzorova S. A., Krylov B. V., Plakhova V. B. Issledovanie vliyaniya ingibitora src-kinazy pp2 na sposobnost uabaina modulirovat medlennye natrievye kanaly [Investigation of src-kinase inhibitor pp2 effects on modulation of slow sodium channels by ouabain]. Sensornye sistemy [Sensory systems]. 2017. V. 31(1). P. 16-21 (in Russian).

References:

  • Plakhova V.B., Podzorova S.A., Mishchenko I.V., Bagraev N.T., Klyachkin L.E., Malyarenko A.M., Romanov V.V., Krylov B.V. Probable effects of infrared irradiation on sensory neuron membrane // Sensorniye Sistemy. 2003. V. 17. N 1. P. 24–31. [in Russian]
  • Almers W. Gating currents and charge movements in excitable membranes // Rev. Physiol. Biochem. Pharmacol. 1978. V. 82. P. 97–190.
  • Borovikova L., Borovikov D., Ermishkin V., Revenko S. The resistance of cutaneous feline C- ber mechano-heat- sensitive unit termination to tetrodotoxin and its possible relation to tetrodotoxin-resistant sodium channels // Primary Sensory Neuron. 1997. V. 2. N 1. P. 65–75.
  • Cardenas C.G., Del Mar L.P., Cooper B.Y., Scroggs R.S. 5HT4 receptors couple positively to tetrodotoxin-insensitive sodium channels in a subpopulation of capsaicin-sensitive rat sensory neurons // J. Neuroscience. 1997. V. 17. N 19. P. 7181–7189.
  • 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. N 4. P. 39–56.
  • 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 // P ügers Arch. 1981. V. 391. N 1. P. 85–100.
  • Hanke J.H., Gardner J.P., Dow R.L., Changelian P.S., Brissette W.H., Weringer E.J., Pollok B.A., Connelly P.A. Discovery of a novel, potent, and Src family-selective tyrosine kinase inhibitor. Study of Lck- and FynT-dependent T cell activation // J. Biol Chem. 1996. V. 271. N 2. P. 695–701.
  • Hodgkin A.L., Huxley A.F. Currents carried by sodium and potassium ions through the membrane of the giant axon of Loligo // J. Physiol. 1952a. V. 116. N 4. P. 449–472.
  • Hodgkin A.L., Huxley A.F. The dual effect of membrane potential on sodium conductance in the giant axon of Loligo // J. Physiol. 1952b. V. 116. N 4. P. 497–506.
  • Hodgkin A.L., Huxley A.F. A quantitative description of membrane current and its application to conduction and excitation in nerve // J. Physiol. 1952c. V. 117. N 4. P. 500–544.
  • Kostyuk P.G., Krishtal O.A., Pidoplichko V.I. Effect of internal uoride and phosphate on membrane currents during intracellular dialysis of nerve cells // Nature. 1975. V. 257. N 5528. P. 691–693.
  • Krylov B., Derbenev A., Podzorova S., Lyudyno M., Kuz‘min A., Izvarina N. Morphine decreases the voltage sensitivity of slow sodium channels // Neurosci. Behav. Physiol. 2000. V. 30. N 4. P. 431–439.
  • Liang M., Tian J., Liu L., Pierre S., Liu J., Shapiro J., Xie Z.J. Identi cation of a pool of non-pumping Na+, К+- АТPase // J. Biol. Chem. 2007. V. 282. N 14. P. 10585–10593.
  • 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+, К+-АТPase by endogenous ouabain and low-power infrared radiation leads to pain relief // Medicinal Chemistry. 2012. V. 8. N 1. P. 33–39.
  • Rogachevskii I.V., Shelykh T.N., Podzorova S.A., Krylov B.V., Plakhova V.B. Ab initio conformational analysis of marinobufagenin molecule and molecular targets of the action of cardiotonic steroids // Russian Journal of Organic Chemistry. 2015. V. 51. N 11. P. 1620–1626.
  • Thomas S.M., Brugge J.S. Cellular functions regulated by Src family kinases // Annu. Rev. Cell. Dev. Biol. 1997. V. 13. P. 513–609.
  • Xie Z., Askari A. Na+, К+-АТPase as a signal transducer // Eur. J. Biochem. 2002. V. 269. N 10. P. 2434–2439.
  • Yachnev I.L., Plakhova V.B., Podzorova S.A., Shelykh T.N., Rogachevsky I.V., Krylov B.V. Mechanism of pain relief by low-power infrared irradiation: ATP is an IR-target molecule in nociceptive neurons // Medicinal Chemistry. 2012. V. 8. N 1. P. 14–21.
  • Yachnev I.L., Shelykh T.N., Podzorova S.A., Rogachevskii I.V., Krylov B.V., Plakhova V.B. Possible molecular effect related to the reception of low-intensity IR radiation: role of Src- kinase // Technical Physics. 2016. V. 61. N 6. P. 929–933.
  • Zhang S.B., Malmersjo S., Li J., Ando H., Aizman O., Uhlen P., Mikoshiba K., Aperia A. Distinct role of the N-terminal tail of the Na+, К+-АТPase catalytic subunit as a signal transducter // J. Biol. Chem. 2006. V. 281. N 31. P. 21954–21962.