Potential roles of β3-adrenergic receptor in heart rate regulation via sinus node activity and local adipocyte metabolism

Figures

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  Fig. 1. mRNA expression patterns of β-adrenergic receptor (β-AR) subtypes in mouse cardiac regions. Expression levels of β1-AR (Adrb1), β2-AR (Adrb2), and β3-AR (Adrb3) in the sinus node (SN), atrial myocardium (AM), and ventricular myocardium (VM). n = 6–10. *P < 0.05 vs SN (one-way ANOVA followed by Games–Howell post hoc test).

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  Fig. 2. Effect of a selective β3-AR agonist on heart rate. A. Representative electrocardiogram recordings before and after administration of propranolol, a β1- and β2-AR antagonist, and BRL 37344, a selective β3-AR agonist, in anaesthetised mice. B. Mean heart rate before and after the administrations. C. Mean PR intervals before and after the administrations. n = 9–10. *P < 0.05 vs. baseline, †p < 0.05 vs. propranolol (repeated-measures ANOVA with Holm-adjusted post hoc comparisons).

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  Fig. 3. Effect of BRL 37344, a selective β3-AR agonist, on heart rate. A. Representative photographs of the right atrial preparation used for extracellular potential recording. B. Representative traces of extracellular potential recordings in baseline, selective β3- and non-selective β-adrenergic stimulation conditions. C. Mean sinus node rate before and after administration of BRL 37344, a selective β-3AR agonist, and subsequent isoproterenol, a non-selective β-AR agonist. n = 7, *P < 0.05 vs. baseline and † P < 0.05 vs. BRL 37344 (repeated-measures ANOVA with Holm-adjusted post hoc comparisons).

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  Fig. 4. Representative micrographs showing β3-AR distribution in the sinus node region and neighbouring atrial myocardium. (A) β3-AR expression is observed in adipocytes surrounding the HCN4-positive sinus node region. (B) No expression of HCN4 or β3-AR is detected in the atrial myocardium, whereas β3-AR is expressed modestly in HCN4-positive pacemaker cells and prominently in adipose tissue. (C) Lipid deposits, indicated by arrowheads, are observed in regions adjacent to the sinus node. The boxed area in the left micrograph is shown at higher magnification. n = 6 biological replicates.

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  Fig. 5. β-AR expression across cell types in the murine sinus node revealed by single-nucleus RNA sequencing. (A) Two-dimensional UMAP plot showing cell clusters identified from analysis of the GSE130710 dataset, including 5357 nuclei isolated from sinus node regions of 16 mice. (B) Centred and scaled expression of marker genes defining the indicated cell types. (C) Feature plots showing the distribution of β1-AR (Adrb1), β2-AR (Adrb2), and β3-AR (Adrb3) transcripts across clusters.