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β‐Adrenergic and Muscarinic Cholinergic Receptor Densities in the Human Sinoatrial Node:
Author(s) -
RODEFELD MARK D.,
BEAU SCOTT L.,
SCHUESSLER RICHARD B.,
BOINEAU JOHN P.,
SAFFITZ JEFFREY E.
Publication year - 1996
Publication title -
journal of cardiovascular electrophysiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.193
H-Index - 138
eISSN - 1540-8167
pISSN - 1045-3873
DOI - 10.1111/j.1540-8167.1996.tb00479.x
Subject(s) - sinoatrial node , medicine , muscarinic acetylcholine receptor , endocrinology , radioligand , receptor , adrenergic , adrenergic receptor , muscarinic acetylcholine receptor m2 , cholinergic , heart rate , blood pressure
Autonomic Receptors in Human Sinus Node. 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 [ 125 I] iodocyanopindolol. β 2 ‐Adrenergic receptors were determined by measuring the amount of radioactivity bound to sections incubated with radioligand in the presence of the highly β 1 ‐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 β 1 ‐ (4.2. P < 0.002), β 2 ‐ (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 β 2 ‐subtype is predominant in both regions. the β 2 ‐subtype, however, is > 2.5‐fold more abundant in the sinoatrial node than in atrial myocardium. The relatively high β 2 ‐receptor density in the human sinoatrial node is consistent with physiologic studies that implicate this receptor in regulating cardiac chronotropism.