ATP inhibits the spontaneous contractility of atria in rats

A.A. Zverev^*, T.A. Anikina^**, N.G. Iskakov^***, N.V. Leonov^****, T.L. Zefirov^*****

Kazan Federal University, Kazan, 420008 Russia

E-mail: ^*Alekcei5@rambler.ru, ^**TAAnikina@kpfu.ru, ^***nikitaiskakov1992@mail.ru, ^****leo_0610-1993@mail.ru, ^*****zefirovtl@mail.ru

Received July 10, 2018

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Abstract

ATP is a multifunctional nucleotide. In recent years, strong evidence has accumulated that ATP may participate in intercellular signaling, where ATP acts as a cotransmitter. ATP participation in the regulation of physiological functions in the organism is carried out through specific purinoreceptors, which were found in many tissues of the organism, including the heart. The aim of our research was to study the role of ATP at different concentrations on the parameters of electrical activity and the contractility of the myocardium of the right atrium of rats with a preserved sinus node.

The experiments were performed on the myocardium of the right atrium of rats with spontaneous activity. Isometric reduction and electrical activity of the drugs were recorded.

ATP at the concentration of 10^–8 M caused no significant changes in the parameters under study. ATP at the concentration of 10^–7 M caused two-phase changes in the amplitude-time parameters of myocardial contractility and electrical activity of the right atrium myocardium. In the first minutes of the experiment, ATP caused an increase in the frequency and strength of myocardium contraction and the duration of the action potential at the level of 20, 50, and 90% repolarization. By the 15th minute, the studied parameters were restored. ATP at the concentration of 10^–6 M caused a negative inotropic and chronotropic effect, through the activation of adenosine receptors.

Keywords: purinoreceptors, ATP, action potential, myocardial contractility

Figure Captions

Fig. 1. Effect of ATP (10^–7 М) on the strength (а) and frequency of spontaneous contraction of the right atrium myocardium (b – in the 2nd minute of the experiment, c – in the 29th minute of the experiment).

Fig. 2. Effect of ATP (10^–7 М) on the AP parameters (a) and the frequency of spontaneous contraction of the right atrium myocardium (b – in the 4th minute of the experiment, c – in the 15th minute of the experiment).

References

1. Champe P.C., Harvey R.A., Ferrier D.R. Lippincott's Illustrated Reviews: Biochemistry. Philadelphia, Lippincott Williams and Wilkins, 2004. 608 p.

2. Ralevic V. Burnstock G. Roles of P2-purinoceptors in the cardiovascular system. Circulation, 1991, vol. 84, no. 1, pp. 1–14. doi: 10.1161/01.CIR.84.1.1.

3. Burnstock G. Purinergic nerves. Pharmacol. Rev., 1972, vol. 24, no. 3, pp. 509–581.

4. White T.D. Characteristics of neuronal release of ATP. Prog. Neuro-Psychopharmacol. Biol. Psychiatry, 1984, vol. 8, nos. 4–6, pp. 487–493. doi: 10.1016/0278-5846(84)90005-8.

5. Zimmermann H. Signaling via ATP in the nervous system. Trends Neurosci., 1994, vol. 17, no. 10, pp. 420–426. doi: 10.1016/0166-2236(94)90016-7.

6. Forrester T. Release of ATP from heart. Presentation of a release model using human erythrocyte. Ann. N. Y. Acad. Sci., 1990, vol. 603, pp. 335–352. doi:10.1111/j.1749-6632.1990.tb37684.x.

7. Katsuragi T., Tokunaga T., Ohba M., Sato C., Furucawa T Implication of ATP released from atrial, but not papillary, muscle segments of guinea-pig by isoproterenol and forskolin. Life Sci., 1993, vol. 53, no. 11, pp. 961–967. doi: 10.1016/0024-3205(93)90449-D.

8. Abbracchio M.P., Burnstock G., Boeynaems J.M, Barnard E.A., Boyer J.L., Kennedy C., Knight G.E., Fumagalli M., Gachet C., Jacobson K.A., Weisman G.A. International Union of Pharmacology LVIII: Up­date on the P2Y G protein-coupled nucleotide receptors: from molecular mechanisms and pathophysiology to therapy. Trends Pharmacol. Sci., 2003, vol. 58, no. 3, pp. 281–341.

9. Ralevic V. Receptors for purines and pyrimidines. Pharmacol. Rev., 1998, vol. 50, no. 3, pp. 413–492.

10. Vassort G. Adenosine 5'-triphosphate: A P2-purinergic agonist in the myocardium. Physiol. Rev., 2001, vol. 81, no. 2, pp. 767–806. doi: 10.1152/physrev.2001.81.2.767.

11. Ennion S., Hagan S., Evans R.J. The role of positively charged amino acids in ATP recognition by human P2X1 receptors. J. Biol. Chem., 2000, vol. 275, no. 38, pp. 29361–29367. doi: 10.1074/jbc.M005481200.

12. Boehm S., Kubista H. Fine tuning of sympathetic transmitter release via ionotropic and metabotropic presynaptic receptors. Pharmacol. Rev., 2002, vol. 54, no. 1, pp. 43–99.

13. < > I.P., Zapadnyuk V.I., Zakhariya E.A., Zapadnyuk B.V. Laboratornye zhivotnye. Razvedenie, soderzhanie, ispol'zovanie v eksperimente [Laboratory Animals. Breeding, Housing, and Use in Experiments]. Kiev, Vishcha Shk., 1983. 383 p. (In Russian){cke_protected}{C}%3C!%2D%2D%20%20%2D%2D%3E-->

    Hansen M.A, Bennett M.R, Barden J.A. Distribution of purinergic P2X receptors in the rat heart. J. Auton. Nerv. Syst., 1999, vol. 78, no. 1, pp. 1–9. doi: 10.1016/S0165-1838(99)00046-6.

14. Hara Y., Nakaya H. Dual effects of extracellular ATP on the muscarinic acetylcholine receptor-operated K+ current in guinea-pig atrial cells. Eur. J. Pharmacol., 1997, vol. 324, nos. 2–3, pp. 295–303. doi: 10.1016/S0014-2999(97)00088-5.

15. Anikina T.A., Bilalova G.A., Zverev A.A., Sitdikov F.G. Effect of ATP and its analogs on contractility of rat myocardium during ontogeny. Bull. Exp. Biol. Med., 2007, vol. 144, no. 1, pp. 4–7. doi: 10.1007/s10517-007-0239-z.

16. Gessi S., Merighi S., Varani K., Borea P.A. Adenosine receptors in health and disease. Adv. Pharmacol., 2011, vol. 61, pp. 41–75. doi: 10.1016/B978-0-12-385526-8.00002-3.

For citation: Zverev A.A., Anikina T.A., Iskakov N.G., Leonov N.V., Zefirov T.L. ATP inhibits the spontaneous contractility of atria in rats. Uchenye Zapiski Kazanskogo Universiteta. Seriya Estestvennye Nauki, 2018, vol. 160, no. 4, pp. 558–567. (In Russian)

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