Regenerative potential of spiny mice (Acomys cahirinus) manifests in pacemaker myocardium expansion and in predominance of noncanonical, IK,ACH-independent pathway of the cholinergic regulation of the cardiac pacemaking

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Abstract

Spinny mice (Acomys cahirinus) exhibit the ability to regenerate damaged myocardium and functional indices of the heart demonstrated in various models of cardiac pathologies. Cardioregenerative abilities of Acomys are associated with partial preservation of the neonatal phenotype of cardiac tissue in adult animals. An electrophysiology of the untypical Acomys myocardium is extremely poorly elucidated. In the presented study, the bioelectric properties; as well as the mechanisms of parasympathetic control of the pacemaker of the heart of spiny mice was investigated using ECG in vivo recording, registration of action potential and mapping of activation pattern of the supraventricular myocardium. It was found that pacemaker-type action potentials are detected in a significant part of the right atrium while primary activation occurs approximately in 41% or the atrium surface in Acomys. Cholinergic stimulation causes pronounced suppression of automaticity and induces changes in the pattern of activation of the pacemaker myocardium of spiny mice. Cholinergic inhibition of automaticity in Acomys is mediated by IKAch-independent mechanisms. Thus, the cardioregenerative potential of spiny mice manifests in delocalization and non-classical regulation of the cardiac pacemaker.

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About the authors

V. S. Kuzmin

Federal State Budgetary Institution national medical research centre of cardiology named after academician E.I. Chazov of the Ministry of Health of the Russian Federation; Moscow State University

Author for correspondence.
Email: ku290381@mail.ru

Moscow State University, biological faculty, department of human and animals physiology

Russian Federation, Moscow; Moscow

Yu. V. Egorov

Federal State Budgetary Institution national medical research centre of cardiology named after academician E.I. Chazov of the Ministry of Health of the Russian Federation

Email: ku290381@mail.ru
Russian Federation, Moscow

A. M. Karhov

Federal State Budgetary Institution national medical research centre of cardiology named after academician E.I. Chazov of the Ministry of Health of the Russian Federation; Moscow State University

Email: ku290381@mail.ru

Moscow State University, biological faculty, department of human and animals physiology

Russian Federation, Moscow; Moscow

M. A. Boldyreva

Federal State Budgetary Institution national medical research centre of cardiology named after academician E.I. Chazov of the Ministry of Health of the Russian Federation; HSE University

Email: ku290381@mail.ru

Faculty of Biology and Biotechnology

Russian Federation, Moscow; Moscow

E. V. Parfyonova

Federal State Budgetary Institution national medical research centre of cardiology named after academician E.I. Chazov of the Ministry of Health of the Russian Federation

Email: ku290381@mail.ru

Corresponding Member of the RAS

Russian Federation, Moscow

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2. Fig. 1. A. Representative example of ECG (equivalent to standard lead II) and electrocardiographic characteristics of Acomys. JT is the interval from the peak of the J-wave to the moment the curve returns to the isobaseline (T-end). B. The ratio of QT and RR intervals in spiny mice. C. Representative examples of electrically evoked action potentials (AP) of the working atrial myocardium of Acomys under control conditions and under the action of acetylcholine (Ach). D. Amplitude of atrial AP under control conditions and under the action of acetylcholine. D, E. Duration of atrial AP at the level of 30 (AP30, left) and 90% (AP90, right) of repolarization. LA – left atrium, RA – right atrium. * – p(T)<0.05.

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3. Fig. 2. Right atrial activation pattern and cholinergic modulation of automatic activity in Acomys. A. Localization of puncta (TPA, marked with an asterisk) and the area of ​​primary activation zones (shown in yellow) in the interveinal region (IRC) of the right atrium of the spiny mouse under control (top, right) conditions and under the action of acetylcholine (Ach, 1, 10 μM, bottom). The area of ​​the activated site is indicated as a proportion (%) of the total area of ​​the smooth-walled part of the atrium. An isolated tissue preparation of the right atrium of Acomys and its macroscopic organization are shown at the top left. (R)SVC, (L)SVC – right and left superior (cranial) vena cava, AU – atrial appendage, T – trabeculae of the atrial appendage, CT – terminal cristae, VVCI – valve of the inferior vena cava, ICR – interveinal region; FO – fossa ovalis; IAS – atrial septum. The purple dotted line shows the venous orifices; the blue dotted line shows the edge of the inferior vena cava valve; the black dotted line limits the interveinal region, which includes the pacemaker myocardium. B. Localization of dots and the area of ​​primary activation zones in the right atrium of C57Bl6 mice under control (top) and under the action of Ach (bottom). C. Representative recordings of spontaneous pacemaker action potentials (SPP) recorded in the TPA of the interveinal region of Acomys under control conditions and under the action of Ach. MDP – maximum diastolic potential. D. Representative recordings demonstrating a decrease in the SPP frequency (top) and an unchanged MDP (bottom) in the pacemaker myocardium of spiny mice under the action of Ach. D. Representative examples of recordings of the nonlinear phase of the initial depolarization of the SPD in spiny mice in the control and under the action of Ach. E. The frequency of the SPD (left) and the area of ​​the primary activation zones (right, STP, % of the total area of ​​the smooth-walled part of the atrium), recorded in isolated tissue preparations of the atrium of Acomys and C57Bl6 mice under control conditions and under the action of Ach. # – p<0.05 (Ach vs control, ANOVA); & – p<0.05 (Acomys vs C57Bl6, ANOVA).

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