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

Yukihiro Harada, Chih Chi Kao, Tomoe Ueyama, Alphonse Boché, Morshedul Alam Azad Khandaker, Shu Nakao, Teruhisa Kawamura

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Article in The journal of physiological sciences : JPS, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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7 authors.

Yukihiro HaradaCollege of Life Sciences, Ritsumeikan University, 1-1-1 Nojihigashi, Kusatsu, Shiga 525-8577, Japan.

Chih Chi KaoCollege of Life Sciences, Ritsumeikan University, 1-1-1 Nojihigashi, Kusatsu, Shiga 525-8577, Japan; Department of Cardiac Regeneration Biology, National Cerebral and Cardiovascular Center Research Institute, 6-1 Kishibeshinmachi, Suita, Osaka 564-8565, Japan.

Tomoe UeyamaResearch Organization of Science and Technology, Ritsumeikan University, 1-1-1 Nojihigashi, Kusatsu, Shiga 525-8577, Japan.

Alphonse BochéDepartment of Physiology, Tokai University School of Medicine, 143 Shimokasuya, Isehara, Kanagawa 259-1193, Japan.

Morshedul Alam Azad KhandakerDepartment of Physiology, Tokai University School of Medicine, 143 Shimokasuya, Isehara, Kanagawa 259-1193, Japan; The Institute of Medical Sciences, Tokai University, 143 Shimokasuya, Isehara, Kanagawa 259-1193, Japan.

Shu NakaoCollege of Life Sciences, Ritsumeikan University, 1-1-1 Nojihigashi, Kusatsu, Shiga 525-8577, Japan; Research Organization of Science and Technology, Ritsumeikan University, 1-1-1 Nojihigashi, Kusatsu, Shiga 525-8577, Japan; Department of Physiology, Tokai University School of Medicine, 143 Shimokasuya, Isehara, Kanagawa 259-1193, Japan; The Institute of Medical Sciences, Tokai University, 143 Shimokasuya, Isehara, Kanagawa 259-1193, Japan. Electronic address: nakao.shu.s@tokai.ac.jp.

Teruhisa KawamuraCollege of Life Sciences, Ritsumeikan University, 1-1-1 Nojihigashi, Kusatsu, Shiga 525-8577, Japan; Ritsumeikan Global Innovation Research Organization, Ritsumeikan University, 1-1-1 Nojihigashi, Kusatsu, Shiga 525-8577, Japan. Electronic address: kawater@fc.ritsumei.ac.jp.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

β-Adrenergic signalling plays a central role in the regulation of diverse physiological processes, including cardiovascular function. In the heart, β1-adrenergic receptors (β1-ARs) mediate most sympathetic effects on contractility and heart rate, whereas the role of β3-ARs remains poorly understood. Here we investigated the expression and functional significance of β3-ARs in the sinus node (SN), the primary cardiac pacemaker. β3-AR expression showed a clear regional gradient, being highest in adipose tissue associated with the SN, modest in the SN itself, and minimal in atrial and ventricular myocardium. Single-nucleus RNA sequencing further demonstrated enriched β3-AR transcripts in adipocytes within the SN region and modest expression in SN and atrial myocytes. Pharmacological modulation of β3-AR activity influenced heart rate and altered spontaneous firing in isolated right atrial preparations containing the SN. These findings suggest that β3-AR signalling may influence pacemaker activity both directly within the SN and indirectly through local adipose tissue metabolism.

Indexed as

Autonomic regulationCardiac conduction systemHeart rateMetabolismβ-adrenergic receptors

Identifiers

PMID42759187

DOI10.1016/j.jphyss.2026.100101

PMCPMC13613536

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