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Extracellular ATP and β-NAD alter electrical properties and cholinergic effects in the rat heart in age-specific manner

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Abstract

Extracellular ATP and nicotinamide adenine dinucleotide (β-NAD) demonstrate properties of neurotransmitters and neuromodulators in peripheral and central nervous system. It has been shown previously that ATP and β-NAD affect cardiac functioning in adult mammals. Nevertheless, the modulation of cardiac activity by purine compounds in the early postnatal development is still not elucidated. Also, the potential influence of ATP and β-NAD on cholinergic neurotransmission in the heart has not been investigated previously. Age-dependence of electrophysiological effects produced by extracellular ATP and β-NAD was studied in the rat myocardium using sharp microelectrode technique. ATP and β-NAD could affect ventricular and supraventricular myocardium independent from autonomic influences. Both purines induced reduction of action potentials (APs) duration in tissue preparations of atrial, ventricular myocardium, and myocardial sleeves of pulmonary veins from early postnatal rats similarly to myocardium of adult animals. Both purine compounds demonstrated weak age-dependence of the effect. We have estimated the ability of ATP and β-NAD to alter cholinergic effects in the heart. Both purines suppressed inhibitory effects produced by stimulation of intracardiac parasympathetic nerve in right atria from adult animals, but not in preparations from neonates. Also, ATP and β-NAD suppressed rest and evoked release of acetylcholine (ACh) in adult animals. β-NAD suppressed effects of parasympathetic stimulation and ACh release stronger than ATP. In conclusion, ATP and β-NAD control the heart at the postsynaptic and presynaptic levels via affecting the cardiac myocytes APs and ACh release. Postsynaptic and presynaptic effects of purines may be antagonistic and the latter demonstrates age-dependence.

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Abbreviations

ACh:

Acetylcholine

AF:

Atrial fibrillation

AP:

Action potential

APD:

Action potential duration

APD90:

Action potential duration at 90% of repolarization

LA:

Left atrium

NST:

Neostigmine

P1:

1st day of postnatal development

P14:

14st day of postnatal development

P21:

21st day of postnatal development

PV:

Pulmonary vein

RA:

Right atrium

RV:

Right ventricular wall

SAP:

Spontaneous action potential

β-NAD:

β-nicotinamide adenine dinucleotide

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Funding

This study was supported by Russian Science Foundation grant 14-15-00268.

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Authors and Affiliations

  1. Department of Human and Animal Physiology, Lomonosov Moscow State University, Leninskie gory 1, building 12, Moscow, Russia, 119991

    Ksenia B. Pustovit, Viktoria M. Potekhina, Alexandra D. Ivanova, Denis V. Abramochkin & Vlad S. Kuzmin

  2. Department of Physiology, Pirogov Russian National Research Medical University, Ostrovitjanova 1, Moscow, Russia, 117997

    Ksenia B. Pustovit, Denis V. Abramochkin & Vlad S. Kuzmin

  3. Institute of Neuroscience, Kazan State Medial University, Butlerova st. 49, Kazan, Russia, 420012

    Alexey M. Petrov

  4. Laboratory of Biophysics of Synaptic Processes, Kazan Institute of Biochemistry and Biophysics, Federal Research Center “Kazan Scientific Center of RAS”, P. O. Box 30, Lobachevsky Str., 2/31, Kazan, Russia, 420111

    Alexey M. Petrov

  5. Laboratory of Cardiac Physiology, Institute of Physiology, Komi Science Center, Ural Division, Russian Academy of Sciences, Pervomayskaya 50, Syktyvkar, Russia, 167982

    Denis V. Abramochkin

Authors
  1. Ksenia B. Pustovit
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  2. Viktoria M. Potekhina
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  3. Alexandra D. Ivanova
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  4. Alexey M. Petrov
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  5. Denis V. Abramochkin
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  6. Vlad S. Kuzmin
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Contributions

Participated in the study planning: Kuzmin VS.

Performed experiments and data analysis: Pustovit KB, Potekhina VM, Ivanova AD.

Contributed to the discussion and reviewed/edited the manuscript: Petrov AM.

Wrote the manuscript: Abramochkin DV, Kuzmin VS.

Corresponding author

Correspondence to Vlad S. Kuzmin.

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Conflicts of interest

Pustovit KB declares that she has no conflict of interest.

Potekhina VM declares that she has no conflict of interest.

Ivanova AD declares that she has no conflict of interest.

Petrov AM declares that he has no conflict of interest.

Abramochkin DV declares that he has no conflict of interest.

Kuzmin VS declares that he has no conflict of interest.

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This study was approved by Bioethics Committee of Moscow State University.

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Pustovit, K.B., Potekhina, V.M., Ivanova, A.D. et al. Extracellular ATP and β-NAD alter electrical properties and cholinergic effects in the rat heart in age-specific manner. Purinergic Signalling 15, 107–117 (2019). https://doi.org/10.1007/s11302-019-09645-6

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