The role of M3 receptors in regulation of electrical activity deteriorates in the rat heart during ageing
Ageing is a complex process which affects all systems of the organism and therefore changes the environment where the heart is working. In this study we demonstrate the ageing-related changes in the mechanisms of parasympathetic regulation of mammalian heart. Electrophysiological effects produced by...
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| Format: | Article |
| Language: | English |
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Elsevier
2022-01-01
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| Series: | Current Research in Physiology |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2665944121000316 |
| _version_ | 1811188513784201216 |
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| author | Svetlana V. Tapilina Alexandra D. Ivanova Tatiana S. Filatova Pavel A. Galenko-Yaroshevsky Denis V. Abramochkin |
| author_facet | Svetlana V. Tapilina Alexandra D. Ivanova Tatiana S. Filatova Pavel A. Galenko-Yaroshevsky Denis V. Abramochkin |
| author_sort | Svetlana V. Tapilina |
| collection | DOAJ |
| description | Ageing is a complex process which affects all systems of the organism and therefore changes the environment where the heart is working. In this study we demonstrate the ageing-related changes in the mechanisms of parasympathetic regulation of mammalian heart. Electrophysiological effects produced by selective activation of M3-cholinoreceptors were compared in isolated cardiac preparations from young adult (4 months), adult (1 year) and ageing (2 years) rats using sharp glass microelectrode technique. M3-receptors were activated with muscarinic agonist pilocarpine (10-5M) in the presence of selective M2 antagonist AQ-RA741 (10-7M). In atrial and ventricular myocardium from young rats M3 stimulation induced shortening of action potentials(APs), while no significant effect was observed in both elder groups. The main mechanism of M3-induced AP shortening is inhibition of L-type Ca2+ current, estimated using whole-cell patch-clamp. It was negligible in atrial myocytes from ageing animals in comparison with young rats. The loss of sensitivity to stimulation of M3-receptors is due to decrease in M3 gene expression, shown by RT-PCR both in atrial and ventricular samples from ageing rats. Thus, in ageing rat heart M3-receptors are down-regulated and not involved in regulation of electrical activity. |
| first_indexed | 2024-04-11T14:21:10Z |
| format | Article |
| id | doaj.art-60989c4dc8d24617bab89c548b0f948c |
| institution | Directory Open Access Journal |
| issn | 2665-9441 |
| language | English |
| last_indexed | 2024-04-11T14:21:10Z |
| publishDate | 2022-01-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Current Research in Physiology |
| spelling | doaj.art-60989c4dc8d24617bab89c548b0f948c2022-12-22T04:19:04ZengElsevierCurrent Research in Physiology2665-94412022-01-01517The role of M3 receptors in regulation of electrical activity deteriorates in the rat heart during ageingSvetlana V. Tapilina0Alexandra D. Ivanova1Tatiana S. Filatova2Pavel A. Galenko-Yaroshevsky3Denis V. Abramochkin4Department of Human and Animal Physiology, Moscow State University, Leninskiye Gory 1, 12, Moscow, RussiaDepartment of Human and Animal Physiology, Moscow State University, Leninskiye Gory 1, 12, Moscow, RussiaDepartment of Human and Animal Physiology, Moscow State University, Leninskiye Gory 1, 12, Moscow, Russia; Department of Physiology, Pirogov Russian National Research Medical University, Ostrovityanova Str 1, Moscow, Russia; Laboratory of Cardiac Electrophysiology, National Medical Research Center for Cardiology, Moscow, RussiaDepartment of Pharmacology, Kuban’ State Medical University, Sedina Str. 4, Krasnodar, RussiaDepartment of Human and Animal Physiology, Moscow State University, Leninskiye Gory 1, 12, Moscow, Russia; Corresponding author. Biological faculty of the Moscow State University, Department of human and animal physiology, Leninskiye gory, 1, 12, Moscow, Russia.Ageing is a complex process which affects all systems of the organism and therefore changes the environment where the heart is working. In this study we demonstrate the ageing-related changes in the mechanisms of parasympathetic regulation of mammalian heart. Electrophysiological effects produced by selective activation of M3-cholinoreceptors were compared in isolated cardiac preparations from young adult (4 months), adult (1 year) and ageing (2 years) rats using sharp glass microelectrode technique. M3-receptors were activated with muscarinic agonist pilocarpine (10-5M) in the presence of selective M2 antagonist AQ-RA741 (10-7M). In atrial and ventricular myocardium from young rats M3 stimulation induced shortening of action potentials(APs), while no significant effect was observed in both elder groups. The main mechanism of M3-induced AP shortening is inhibition of L-type Ca2+ current, estimated using whole-cell patch-clamp. It was negligible in atrial myocytes from ageing animals in comparison with young rats. The loss of sensitivity to stimulation of M3-receptors is due to decrease in M3 gene expression, shown by RT-PCR both in atrial and ventricular samples from ageing rats. Thus, in ageing rat heart M3-receptors are down-regulated and not involved in regulation of electrical activity.http://www.sciencedirect.com/science/article/pii/S2665944121000316HeartRatAction potentialCalcium currentMuscarinic receptorsAgeing |
| spellingShingle | Svetlana V. Tapilina Alexandra D. Ivanova Tatiana S. Filatova Pavel A. Galenko-Yaroshevsky Denis V. Abramochkin The role of M3 receptors in regulation of electrical activity deteriorates in the rat heart during ageing Current Research in Physiology Heart Rat Action potential Calcium current Muscarinic receptors Ageing |
| title | The role of M3 receptors in regulation of electrical activity deteriorates in the rat heart during ageing |
| title_full | The role of M3 receptors in regulation of electrical activity deteriorates in the rat heart during ageing |
| title_fullStr | The role of M3 receptors in regulation of electrical activity deteriorates in the rat heart during ageing |
| title_full_unstemmed | The role of M3 receptors in regulation of electrical activity deteriorates in the rat heart during ageing |
| title_short | The role of M3 receptors in regulation of electrical activity deteriorates in the rat heart during ageing |
| title_sort | role of m3 receptors in regulation of electrical activity deteriorates in the rat heart during ageing |
| topic | Heart Rat Action potential Calcium current Muscarinic receptors Ageing |
| url | http://www.sciencedirect.com/science/article/pii/S2665944121000316 |
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