Extracellular ATP and β-NAD alter electrical properties and cholinergic effects in the rat heart in age-specific manner
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.
KeywordsHeart Cholinergic effects Postnatal development β-NAD ATP Purine cotransmitters
Action potential duration
Action potential duration at 90% of repolarization
1st day of postnatal development
14st day of postnatal development
21st day of postnatal development
Right ventricular wall
Spontaneous action potential
β-nicotinamide adenine dinucleotide
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.
This study was supported by Russian Science Foundation grant 14-15-00268.
Compliance with ethical standards
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.
This study was approved by Bioethics Committee of Moscow State University.
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