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Functional M3 cholinoreceptors are present in pacemaker and working myocardium of murine heart

  • Cardiovascular Physiology
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Abstract

The presence of M3 cholinoreceptors and their role in mediation of action potential waveform modulation were determined by immunolabeling of receptor proteins and standard microelectrode technique, respectively. The sinoatrial node (SAN), which was determined as a connexin 43 negative area within the intercaval region, the surrounding atrial tissue, and the working ventricular myocardium exhibited labeling of both M3 and M2 receptors. However, the density of M3 and M2 labeling was about twofold higher in the SAN compared to working myocardium. The stimulation of M3 receptors was obtained by application of nonselective M1 and M3 muscarinic agonist pilocarpine (10−5 M) in the presence of selective M2 blocker methoctramine (10−7 M). Stimulation of M3 receptors provoked marked shortening of action potential duration in atrial and ventricular working myocardium. In the SAN, M3 stimulation leads to a significant reduction of sinus rhythm rate accompanied with slowing of diastolic depolarization and increase of action potential upstroke velocity. All electrophysiological effects of selective M3 stimulation were suppressed by specific blocker of M3 receptors 4-DAMP (10−8 M). We conclude that M3 cholinoreceptors are present in pacemaker and working myocardium of murine heart, where they mediate negative cholinergic effects: slowing of sinus rhythm and shortening of action potentials.

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Acknowledgments

This work was supported by the Russian Foundation for Basic Research (12-04-01414, 11-04-00602).

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The authors declare that they have no conflict of interest.

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Authors and Affiliations

  1. Department of Human and Animal Physiology, Moscow State University, Leninskiye Gory, 1, 12, Moscow, Russia

    Denis V. Abramochkin, Svetlana V. Tapilina & Galina S. Sukhova

  2. Kazan Institute of Biochemistry and Biophysics, Russian Academy of Sciences, Kazan, Russia

    Eugen E. Nikolsky & Leniz F. Nurullin

  3. Kazan State Medical University, Kazan, Russia

    Eugen E. Nikolsky

Authors
  1. Denis V. Abramochkin
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  2. Svetlana V. Tapilina
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  3. Galina S. Sukhova
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  4. Eugen E. Nikolsky
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  5. Leniz F. Nurullin
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Correspondence to Denis V. Abramochkin.

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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 - Eur J Physiol 463, 523–529 (2012). https://doi.org/10.1007/s00424-012-1075-1

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  • DOI: https://doi.org/10.1007/s00424-012-1075-1

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