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Cardiotoxins from Cobra Naja oxiana Change the Force of Contraction and the Character of Rhythmoinotropic Phenomena in the Rat Myocardium

  • BIOCHEMISTRY, BIOPHYSICS, AND MOLECULAR BIOLOGY
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Abstract

The study of the influence of cobra Naja oxiana cardiotoxins on the contractility of the rat papillary muscles and its rhythmoinotropic characteristics has shown that the presence of toxins induces a slight contractility decrease in the stimulation frequency range up to 0.1 Hz. In the stimulation frequency range from 0.1 to 0.5 Hz, a positive inotropic effect is found. However, the positive inotropic effect is replaced by a negative one with further increase in the frequency up to 3 Hz. In the presence of cardiotoxins, the positive force–frequency relationship in the region of 1–3 Hz, characteristic of healthy rat myocardium, disappears and the relationship becomes completely negative. L-type calcium channel blocker nifedipine does not affect the changes induced by toxins, while a high concentration (10 mM) of calcium prevents the effects of cardiotoxins on the muscle. The results obtained show that the impairment of the force–frequency relationship occurs long before the development of irreversible damage in the myocardium and may be the first sign of the pathological action of cardiotoxins.

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REFERENCES

  1. Sun, J.J. and Walker, M.J., Actions of cardiotoxins from the southern Chinese cobra (Naja naja atra) on rat cardiac tissue, Toxicon, 1986, vol. 24, no. 3, pp. 233–245.

    Article  CAS  Google Scholar 

  2. Harvey, A.L., Marshall, R.J., and Karlsson, E., Effects of purified cardiotoxins from the Thailand cobra (Naja naja siamensis) on isolated skeletal and cardiac muscle preparations, Toxicon, 1982, vol. 20, no. 2, pp. 379–396.

    Article  CAS  Google Scholar 

  3. Huang, S.J. and Kwan, C.Y., Inhibition by multivalent cations of contraction induced by Chinese cobra venom cardiotoxin in guinea pig papillary muscle, Life Sci., 1996, vol. 59, no. 4, pp. L55–L60. https://doi.org/10.1016/0024-3205(96)00305-0

    Article  Google Scholar 

  4. Gattoni, S., Roe, A.T., Frisk, M., Louch, W.E., Niederer, S.A., and Smith, N.P., The calcium–frequency response in the rat ventricular myocyte: An experimental and modelling study, J. Physiol., 2016, vol. 594, no. 15, pp. 4193–4224. https://doi.org/10.1113/JP272011

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Wang, H.X., Lau, S.Y., Huang, S.J., Kwan, C.Y., and Wong, T.M., Cobra venom cardiotoxin induces perturbations of cytosolic calcium homeostasis and hypercontracture in adult rat ventricular myocytes, J. Mol. Cell. Cardiol., 1997, vol. 29, no. 10, pp. 2759–2770. https://doi.org/10.1006/jmcc.1997.0511

    Article  CAS  PubMed  Google Scholar 

  6. Wang, C.H., Monette, R., Lee, S.C., Morley, P., and Wu, W.G., Cobra cardiotoxin-induced cell death in fetal rat cardiomyocytes and cortical neurons: different pathway but similar cell surface target, Toxicon, 2005, vol. 46, no. 4, pp. 430–440. https://doi.org/10.1016/j.toxicon.2005.06.012

    Article  CAS  PubMed  Google Scholar 

  7. Dubovskii, P.V., Lesovoy, D.M., Dubinnyi, M.A., Konshina, A.G., Utkin, Y.N., Efremov, R.G., and Arseniev, A.S., Interaction of three-finger toxins with phospholipid membranes: comparison of S- and P‑type cytotoxins, Biochem. J., 2005, vol. 387, pp. 807–815. https://doi.org/10.1042/BJ20041814

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Grishin, E.V., Sukhikh, A.P., Adamovich, T.B., and Ovchinnikov, Yu.A., Isolation, properties, and amino acid sequence of two cytotoxins from the venom of the Central Asian cobra Naja naja oxiana, Bioorg. Khim., 1976, vol. 2, no. 8, pp. 1018–1034.

    CAS  Google Scholar 

  9. Nakipova, O.V., Averin, A.S., Evdokimovskii, E.V., Pimenov, O.Y., Kosarski, L., Ignat’ev, D., Anufriev, A., Kokoz, Y.M., Reyes, S., Terzic, A., and Alekseev, A.E., Store-operated Ca2+ entry supports contractile function in hearts of hibernators, PLoS One, 2017, vol. 12, no. 5. e0177469. https://doi.org/10.1371/journal.pone.0177469

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Huang, S.J., Wu, C.K., and Sun, J.J., Positive inotropic and toxic action of direct lytic factor on isolated working guinea pig hearts, Zhongguo Yao Li Xue Bao, 1991, vol. 12, no. 2, pp. 125–131.

    CAS  PubMed  Google Scholar 

  11. Stuyvers, B.D., McCulloch, A.D., Guo, J., Duff, H.J., and ter Keurs, H.E., Effect of stimulation rate, sarcomere length and Ca(2+) on force generation by mouse cardiac muscle, J. Physiol., 2002, vol. 544, no. 3, pp. 817–830. https://doi.org/10.1113/jphysiol.2002.024430

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Li, S., Huang, H., Zhang, M., Wang, W., Xue, S., Gao, Y., Xie, M., Chen, K., Liu, F., and Chen, L., Liguzinediol enhances the inotropic effect of rat hearts via inhibition of protein phosphatase (PP1 and PP2A) activities, J. Cardiovasc. Pharmacol., 2017, vol. 69, no. 4, pp. 236–244. https://doi.org/10.1097/FJC.0000000000000467

    Article  CAS  PubMed  Google Scholar 

  13. Bougis, P.E., Khélif, A., and Rochat, H., On the inhibition of [Na+,K+]-ATPases by the components of Naja mossambica mossambica venom: evidence for two distinct rat brain [Na+,K+]-ATPase activities, Biochemistry, 1989, vol. 28, no. 7, pp. 3037–3043.

    Article  CAS  Google Scholar 

  14. Kwan, C.Y., Kwan, T.K., and Huang, S.J., Effect of calcium on the vascular contraction induced by cobra venom cardiotoxin, Clin. Exp. Pharmacol. Physiol., 2002, vol. 29, no. 9, pp. 823–828. https://doi.org/10.1046/j.1440-1681.2002.03723.x

    Article  CAS  PubMed  Google Scholar 

  15. Wu, P.L., Chiu, C.R., Huang, W.N., and Wu, W.G., The role of sulfatide lipid domains in the membrane pore-forming activity of cobra cardiotoxin, Biochim. Biophys. Acta, 2012, vol. 1818, no. 5, pp. 1378–1385.

    Article  CAS  Google Scholar 

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Funding

The study was partially supported by the Russian Foundation for Basic Research (project no. 18-54-54006).

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Correspondence to A. S. Averin or Yu. N. Utkin.

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Conflict of interests. The authors declare that they have no conflict of interest.

Statement on the welfare of animals. Experiments on animals were performed in accordance with the European Convention for the Protection of Animals, 1986, 86/609/EEC.

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Translated by M. Batrukova

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Averin, A.S., Astashev, M.E., Andreeva, T.V. et al. Cardiotoxins from Cobra Naja oxiana Change the Force of Contraction and the Character of Rhythmoinotropic Phenomena in the Rat Myocardium. Dokl Biochem Biophys 487, 282–286 (2019). https://doi.org/10.1134/S1607672919040094

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