β-Adrenergic and muscarinic cholinergic receptor densities in the human sinoatrial node: Identification of a high β2-adrenergic receptor density

Mark D. Rodefeld, Scott L. Beau, Richard B. Schuessler, John P. Boineau, Jeffrey E. Saffitz

Research output: Contribution to journalArticle

44 Scopus citations

Abstract

The objective of this study was to measure autonomic receptor densities in the human sinoatrial node and adjacent atrial myocardium to gain further insights into autonomic regulation of sinoatrial node function in the human heart. Sinoatrial nodes (n = 9) were acquired from human donors. Quantitative light microscopic autoradiography of radioligand binding sites in tissue sections was used to compare β-adrenergic and muscarinic cholinergic receptor densities within specific tissue compartments of the sinoatrial node and adjacent myocardium. Total β-adrenergic receptors were measured with the nonsubtype selective radioligand [125I]iodocyanopindolol. β2-Adrenergic receptors were determined by measuring the amount of radioactivity bound to sections incubated with radioligand in the presence of the highly β1- selective antagonist CGP-20712A. Specific autoradiographic grain densities were normalized to myocyte area/unit tissue area. Myocytes in the sinoatrial node occupied 47.7% ± 0.1% of the total tissue area compared with 92.8% ± 0.1% in myocardium (P < 0.001). Total specific β-adrenergic receptor density per unit myocyte area was 3.5 ± 0.9 times greater in the sinoatrial node than in myocardium (P < 0.001). The relative densities of β1- (4.2, P < 0.002), β2- (2.6, P < 0.002), and muscarinic (3.3, P < 0.001) receptors were significantly greater in the sinoatrial node than in the atrium. Thus, total β-adrenergic and muscarinic cholinergic receptor densities are > 3- fold higher in the sinoatrial node than adjacent atrial myocardium, reflecting their specialized roles in regulating cardiac rate and rhythm. The β1-subtype is predominant in both regions. The β2-subtype, however, is > 2.5-fold more abundant in the sinoatrial node than in atrial myocardium. The relatively high β2-receptor density in the human sinoatrial node is consistent with physiologic studies that implicate this receptor in regulating cardiac chronotropism.

Original languageEnglish (US)
Pages (from-to)1039-1049
Number of pages11
JournalJournal of Cardiovascular Electrophysiology
Volume7
Issue number11
DOIs
StatePublished - Jan 1 1996

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Keywords

  • autonomic regulation
  • human sinoatrial node
  • muscarinic cholinergic receptors
  • radioligand autoradiography
  • β-adrenergic receptors

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

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