The compound SS-68 attenuates electrophysiological effects of m3 cholinoreceptors stimulation in rat left atrial myocardium
Abstract
In the present study we have investigated influence of SS-68, which has been previously demonstrated to produce potent antiarrhythmic effects in mammalian myocardium, on the electrophysiological effects of selective M3 cholinoreceptors stimulation in rat atrial myocardium. M3 receptors were activated with muscarinic agonist pilocarpine (10 jM) in the presence of highly selective blocker of M2 cholinoreceptors methoctramine (100 nM). In isolated left atrial preparations M3 stimulation produced reduction of action potential duration by 20 ± 2,2% of control duration. SS-68 (10 jM) decreased intensity of action potential shortening more than twice - to 7,9 ± 1,1% of control action potential duration. SS-68 also suppressed action potential shortening produced by pilocarpine in the absence of M2 antagonist. Thus, compound SS-68 attenuates effect of joint activation of M2 and M3 receptors as well as the effect of selective M3 stimulation.
About the Authors
S. K. Bogus
Kuban state medical university
Russian Federation
Russian Federation
D. V. Abramochkin
Lomonosov Moscow state university
Russian Federation
Russian Federation
K. F. Suzdalev
southern Federal university
Russian Federation
Russian Federation
P. A. Galenko-Yaroshevsky
Kuban state medical university
Russian Federation
Russian Federation
References
1. Богус С. К., Галенко-Ярошевский П. А. Исследование антиангинальных свойств производного индола SS-68 // Новые технологии. - 2012. - № 4. - С. 265-269.
2. Богус С. К., Галенко-Ярошевский П. А., Суздалев К. Ф. Антиаритмическая активность производного индола SS-68 при желудочковых и предсердных формах нарушений ритма сердца // Новые технологии. - 2012. - № 4. - С. 274-279.
3. Федоров В. В., Иванова И. А., Глухов А. В. и др. Холинолитическая активность антиаритмического препарата III класса РГ-2 // Кардиология. - 2004. - Т. 44. № 7. - С. 62-66.
4. Федоров В. В., Розенштраух Л. В., Резник А. В. и др. Антиаритмическая активность препарата III класса РГ-2 на ваготонической модели фибрилляции предсердий // Кардиология. - 2004. - Т. 44. № 11. - С. 66-73.
5. Федоров В. В., Шарифов О. Ф, Розенштраух Л. В. и др. Механизм антиаритмического действия нибентана на экспериментальной модели ваготонической фибрилляции предсердий // Кардиология. - 1999. - Т. 39. № 3. - С. 45-56.
6. Abramochkin D. V., Suris M. A., Borodinova A. A. et al. M3 cholinoreceptors: new mediator of acetylcholine action on myocardium // Neurochem. j. - 2008. - Vol. 2. № 1-2. -P. 90-94.
7. Abramochkin D. V., Tapilina S. V., Sukhova G. S. et al. Functional M3 cholinoreceptors are present in pacemaker and working myocardium of murine heart // Pflugers arch. - 2012. -Vol. 464. № 4. - P. 523-529.
8. Bogus S. K., Abramochkin D. V., Galenko-Yaroshevsky P. A. et al. Effects of a new antiarrhythmic drug SS-68 on electrical activity in working atrial and ventricular myocardium of mouse and their ionic mechanisms // J. pharmacol. sci. - 2015. -Vol. 128. № 4. - P. 202-207.
9. Coumel P. Autonomic influences in atrial tachyarrhythmias // J. cardiovasc. electrophysiol. - 1996. - Vol. 7. - P. 999-1007.
10. Dhein S., Van Koppen C. J., Brodde O. Muscarinic receptors in the mammalian heart // Pharmacol. res. - 2001. -Vol. 44. № 3. - P. 161-182.
11. Hang P., Zhao J., Qi J. et al. Novel insights into the pervasive role of M(3) muscarinic receptor in cardiac diseases // Cur. drug. targets. - 2013. - Vol. 14. № 3. - P. 372-377.
12. Hoffman B. F., Cranefield P. F. Electrophysiology of the heart. - New York: McGraw-Hill Book Company Inc., 1960.
13. Shi H., Wang H., Lu Y. et al. Choline modulates cardiac membrane repolarization by activating an M3 muscarinic receptor and its coupled K+ channel // J. membrane biol. - 1999. -Vol. 169. - P. 55-64.
14. Shi H., Wang H., Wang Z. M3 muscarinic receptor activation of a delayed rectifier potassium current in canine atrial myocytes // Life sci. - 1999. - Vol. 64. № 21. - P. 251-257.
15. Wang S., Han H. M., Jiang Y. N. et al. Activation of cardiac M3 muscarinic acetylcholine receptors has cardioprotective effects against ischaemia-induced arrhythmias // Clin. exp. pharmacol. physiol. - 2012. - Vol. 39. № 4. - P. 343-349.
16. Wang H., Lu Y., Wang Z. Function of cardiac M3 receptors // Auton. autac. pharmacol. - 2007. - Vol. 27. - P. 1-11.
17. Wang H., Shi H., Lu Y. et al. Pilocarpine modulates the cellular electrical properties of mammalian hearts by activating a cardiac M3 receptor and a K+ current // Br. j. pharmacol. - 1999. -Vol. 126. - P. 1725-1734.
18. Wang Z., Shi H., Wang H. Functional M3 muscarinic receptors in mammalian hearts // Br. j. pharmacol. - 2004. -Vol. 142. - P. 395-408.
19. Yang B., Lin H., Xu C. et al. Choline produces cytoprotective effects against ischemic myocardial injuries: evidence for the role of cardiac M3 subtype muscarinic acetylcholine receptors // Cel. physiol. biochem. - 2005. - Vol. 16. № 4 - 6. - P. 163-174.
Review
For citations:
Bogus S.K., Abramochkin D.V., Suzdalev K.F., Galenko-Yaroshevsky P.A. The compound SS-68 attenuates electrophysiological effects of m3 cholinoreceptors stimulation in rat left atrial myocardium. Kuban Scientific Medical Bulletin. 2016;(2):36-39. (In Russ.)
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