Extracellular action potentials of ventricular cardiomyocytes in the heart isolated from rats kept on a high-fat/high-sucrose diet

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Abstract

Rats kept on a high-fat/high-sucrose diet (HFSD) for 10-12 weeks demonstrated the development of hyperglycemia and signs of visceral obesity. Compared to the control, extracellular action potentials (eAP) of subepicardial myocytes of the left ventricle (LV) of HFSD rats characterized by a significantly increased fraction of signals with a pronounced afterhyperpolarization (AHP) phase and an accelerated decline. Local delivery of apamin (a blocker of low-conductivity Ca²⁺-dependent K+ channels (IKCa, SK channels) to the eAP registration cite at a concentration of 500 nM in the solution inside the pipette was accompanied by suppression of the AHP phase and prolongation of the eAP decline. The obtained data suggest that HFSD leads to an increase in the expression and/or activity of SK channels and, as a result, to the development of AHP and shortening of eAP in epicardial cardiomyocytes of the LV of the rat heart.

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About the authors

I. V. Kubasov

Sechenov Institute of Evolutionary Physiology and Biochemistry, Russian Academy of Sciences

Email: botanik2407@gmail.com
Russian Federation, Saint Petersburg

A. V. Stepanov

Sechenov Institute of Evolutionary Physiology and Biochemistry, Russian Academy of Sciences

Author for correspondence.
Email: botanik2407@gmail.com
Russian Federation, Saint Petersburg

Yu. A. Filippov

Sechenov Institute of Evolutionary Physiology and Biochemistry, Russian Academy of Sciences

Email: botanik2407@gmail.com
Russian Federation, Saint Petersburg

O. Yu. Karnishkina

Sechenov Institute of Evolutionary Physiology and Biochemistry, Russian Academy of Sciences

Email: botanik2407@gmail.com
Russian Federation, Saint Petersburg

A. A. Panov

Sechenov Institute of Evolutionary Physiology and Biochemistry, Russian Academy of Sciences

Email: botanik2407@gmail.com
Russian Federation, Saint Petersburg

M. G. Dobretsov

Sechenov Institute of Evolutionary Physiology and Biochemistry, Russian Academy of Sciences

Email: botanik2407@gmail.com
Russian Federation, Saint Petersburg

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Supplementary files

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2. Fig. 4. Changes in the membrane potential of mitochondria in mussel hemocytes under the influence of adrenaline (1 μM and 10 μM) for 5 min (a) and 30 min (b). * – reliable relative to the control at p ≤ 0.05 (n = 10)Fig. 1. Representative examples of continuous recording of autorhythmic eAP1 (a) and examples of individual profiles of normalized eAP1 (b) and eAP2 (c) of cardiomyocytes from the hearts of control rats. The profiles of individual eAPs were normalized to the value of their first negative peak (P1). P2 is the label of the second negative peak of eAP2. Dashed lines show examples of signals accompanied by the AHP phase (afterhyperpolarization). Note that the VPD2 indicated by the dashed line, although it does not have a distinct second negative peak, is characterized by a pronounced kink at the decline of its single negative peak (arrow) and is therefore also classified as VPD2.

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3. Fig. 2. Average characteristics of LV subepicardial eAP in the hearts of control (10 hearts, white columns) and HFSD (9 hearts, gray columns) rats. (a) – Proportion of eAP1 (eAP1) in relation to all recorded eAPs. (b) – Proportion of eAP1 without SG (eAP1AHP=0) in relation to all recorded eAP1s. (c) – Amplitude of SG of eAP1. (d) – T₉₀ of eAP1. (e) – P2/P1 ratio in eAP2 (eAP2). (f) – Proportion of eAP2 without SG (eAP2AHP=0) in relation to all recorded eAP2s. (g) – Amplitude of SG of eAP2. (h) – T₉₀ of eAP2. * – Student’s t-test, p < 0.05; # – Mann–Whitney U test, p < 0.05

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4. Fig. 3. Relationships between the characteristics of the LV subepicardium vAP in individual hearts of control (white symbols, n = 10) and LVSD (black symbols, n = 9) rats. Each symbol represents the average of all vAP1 (n = 4 – 12) or vAP2 (n = 14 – 46) recordings of a given signal type performed in a given heart.

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5. Fig. 4. Examples of changes in the profiles of normalized vPD1 and vPD2, without SG (a, b) and with pronounced SG (c, d) during continuous recording using a micropipette containing apamin. In each of the graphs, the interval between the shown vPD tracks is 5-10 min. The tracks of the signals recorded immediately after the first contact of the pipette with the myocyte and after 30 min of recording are shown by dashed lines.

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6. Fig. 5. Suppression of the SG of vPD1 (a) and vPD2 (b) during a 30-minute recording with a micropipette with PTA depending on the initial amplitude of the SG of the recorded signal. In the figures, each symbol represents an individual recording from an LV cardiomyocyte of the hearts of control (white symbols; (a) – 3 rats, 9 measurements; (b) – 4 rats, 12 measurements) or HFSD (black symbols; (a) – 3 rats, 8 measurements; (b) – 4 rats, 9 measurements) rats. Solid lines are regression lines calculated for all (control and HFSD) data presented in the figure. The parameters of the regression lines are presented in the text.

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7. Fig. 6. Parameters of vPD1 and vPD2 of VZSD rats at the beginning of recording and 30 minutes after the beginning of apamin application: (a) – T₉₀ vPD1; (b) – amplitude of SG vPD1; (c) – T₉₀ vPD2; (d) – amplitude of SG vPD2. (a, b) – 3 rats, 8 measurements; (c, d) – 4 rats, 9 measurements). * – paired Student's t-test, p < 0.05; # – paired Wilcoxon test, p < 0.05.

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