Possible physiological function of endogenous ouabain
DOI:
https://doi.org/10.33910/2687-1270-2021-2-1-96-101Keywords:
nociceptive neurons, NaV1.8 channels, patch-clamp method, organotypic nerve culture method, confocal laser scanning microscopy, endogenous ouabainAbstract
Our results suggest that endogenous ouabain triggers two different signaling processes. The first, fast process, modulates the activation gating device of the NaV1.8 channels, thereby reducing their functional activity. The second, slow process, decreases the density of NaV1.8 channels in the membrane of the primary sensory neuron. We assume that in this case, endogenous ouabain triggers a downstream cascade leading to a decrease in the expression of the SCN10A gene that produces NaV1.8 channels. It can be concluded that endogenous ouabain, when it interacts with the primary sensory neuron, performs important function of modulating functional activity of NaV1.8 channels. The practical result of the study was the assumption that the delivery of ouabain as a drug substance to the membrane of a nociceptive neuron in nanomolar concentration should lead to a safe and effective antinociceptive action of this agent at the organismal level.
References
Almers, W. (1978) Gating currents and charge movements in excitable membranes. In: Reviews of Physiology, Biochemistry and Pharmacology. Vol. 82. Berlin: Springer Publ., pp. 96–190. https://www.doi.org/10.1007/BFb0030498 (In English)
Askari, A. (2019) The sodium pump and digitalis drugs: Dogmas and fallacies. Pharmacology Research & Perspectives, vol. 7, no. 4, article e00505. https://www.doi.org/10.1002/prp2.505 (In English)
Cui, X., Xie, Z. (2017) Protein interaction and Na/K-ATPase-mediated signal transduction. Molecules, vol. 22, no. 6, article 990. https://www.doi.org/10.3390/molecules22060990 (In English)
Hamill, O. P., Marty, A., Neher, E. et al. (1981) Improved patch-clamp techniques for high-resolution current recording from cells and cell-free membrane patches. Pflügers Archiv — European Journal of Physiology, vol. 391, no. 2, pp. 85–100. https://www.doi.org/10.1007/BF00656997 (In English)
Hamlyn, J. M., Blaustein, M. P., Bova, S. et al. (1991) Identification and characterization of a ouabain-like compound from human plasma. Proceedings of the National Academy of Sciences of the United States of America, vol. 88, no. 14, pp. 6259–6263. https://www.doi.org/10.1073/pnas.88.14.6259 (In English)
Kawamura, A., Guo, J., Itagaki, Y. et al. (1999) On the structure of endogenous ouabain. Proceedings of the National Academy of Sciences of the United States of America, vol. 96, no. 12, pp. 6654–6659. https://www.doi.org/10.1073/pnas.96.12.6654 (In English)
Kometiani, P., Li, J., Gnudi, L. et al. (1998) Multiple signal transduction pathways link Na+/K+-ATPase to growth-related genes in cardiac myocytes: The roles of Ras and mitogen-activated protein kinases. Journal of Biological Chemistry, vol. 273, no. 24, pp. 15249–15256. https://www.doi.org/10.1074/jbc.273.24.15249 (In English)
Krylov, B. V., Derbenev, A. V., Podzorova, S. A. et al. (1999) Morfin umen’shaet chuvstvitelnost’ k potentsialu medlennykh natrievykh kanalov [Morphine decreases the voltage sensitivity of the slow sodium channels]. Rossiiskij fiziologicheskij zhurnal imeni I. M. Sechenova — Russian Journal of Physiology, vol. 85, no. 2, pp. 225–236. (In Russian)
Krylov, B. V., Rogachevskii, I. V., Shelykh, T. N., Plakhova, V. B. (2017) Frontiers in pain science. Vol. 1. New non-opioid analgesics: Understanding molecular mechanisms on the basis of patch-clamp and chemical studies. Sharjah: Bentham Science Publ., 203 p. (In English)
Lichtstein, D., Ilani, A., Rosen, H. et al. (2018) Na+, K+-ATPase signaling and bipolar disorder. International Journal of Molecular Sciences, vol. 19, no. 8, article 2314. https://www.doi.org/10.3390/ijms19082314 (In English)
Lopatina, E. V., Yachnev, I. L., Penniyaynen, V. A. et al. (2012) Modulation of signal-transducing function of neuronal membrane Na+,K by endogenous ouabain and low-power infrared radiation leads to pain relief. Medicinal Chemistry, vol. 8, no. 1, pp. 33–39. https://www.doi.org/10.2174/157340612799278531 (In English)
Penniyaynen, V. A., Plakhova, V. B., Rogachevskii, I. V. et al. (2019) Molecular mechanisms and signaling by comenic acid in nociceptive neurons influence the pathophysiology of neuropathic pain. Pathophysiology, vol. 26, no. 3–4, pp. 245–252. https://www.doi.org/10.1016/j.pathophys.2019.06.003 (In English)
Plakhova, V. B., Penniyaynen, V. A., Yachnev, I. V. et al. (2019) Src kinase controls signaling pathways in sensory neuron triggered by low-power infrared radiation. Canadian Journal of Physiology and Pharmacology, vol. 97, no. 5, pp. 400–406. https://www.doi.org/10.1139/cjpp-2018-0602 (In English)
Skou, J. C. (1957) The influence of some cations on an adenosine triphosphatase from peripheral nerves. Biochimica et Biophysica Acta, vol. 23, pp. 394–401. https://www.doi.org/10.1016/0006-3002(57)90343-8 (In English)
Xie, Z., Askari, A. (2002) Na+/K+-ATPase as a signal transducer. European Journal of Biochemistry, vol. 269, no. 10, pp. 2434–2439. https://www.doi.org/10.1046/j.1432-1033.2002.02910.x (In English)
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Copyright (c) 2021 Valentina A. Penniyaynen, Vera B. Plakhova, Svetlana A. Podzorova, Stanislav G. Terekhin, Boris V. Krylov

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