Rodefeld M D, Beau S L, Schuessler R B, Boineau J P, Saffitz J E
Department of Pathology, Washington University School of Medicine, St. Louis, MO 63110, USA.
J Cardiovasc Electrophysiol. 1996 Nov;7(11):1039-49. doi: 10.1111/j.1540-8167.1996.tb00479.x.
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 beta-adrenergic and muscarinic cholinergic receptor densities within specific tissue compartments of the sinoatrial node and adjacent myocardium. Total beta-adrenergic receptors were measured with the nonsubtype selective radioligand [125I]iodocyanopindolol. beta 2-Adrenergic receptors were determined by measuring the amount of radioactivity bound to sections incubated with radioligand in the presence of the highly beta 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 beta-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 beta 1-(4.2, P < 0.002), beta 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 beta-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 beta 1-subtype is predominant in both regions. The beta 2-subtype, however, is > 2.5-fold more abundant in the sinoatrial node than in atrial myocardium. The relatively high beta 2-receptor density in the human sinoatrial node is consistent with physiologic studies that implicate this receptor in regulating cardiac chronotropism.
本研究的目的是测量人类窦房结及相邻心房心肌中的自主神经受体密度，以进一步深入了解人类心脏中窦房结功能的自主神经调节。从人类供体获取窦房结（n = 9）。使用组织切片中放射性配体结合位点的定量光学显微镜放射自显影术，比较窦房结和相邻心肌特定组织区域内的β-肾上腺素能和毒蕈碱胆碱能受体密度。用非亚型选择性放射性配体[125I]碘氰吲哚洛尔测量总β-肾上腺素能受体。通过测量在高β1选择性拮抗剂CGP - 20712A存在下与放射性配体孵育的切片上结合的放射性量来测定β2-肾上腺素能受体。将特定的放射自显影颗粒密度归一化为心肌细胞面积/单位组织面积。窦房结中的心肌细胞占总组织面积的47.7%±0.1%，而心肌中的心肌细胞占92.8%±0.1%（P < 0.001）。每单位心肌细胞面积的总特异性β-肾上腺素能受体密度在窦房结中比在心肌中高3.5±0.9倍（P < 0.001）。窦房结中β1-（4.2，P < 0.002）、β2-（2.6，P < 0.002）和毒蕈碱（3.3，P < 0.001）受体的相对密度显著高于心房。因此，窦房结中总β-肾上腺素能和毒蕈碱胆碱能受体密度比相邻心房心肌高3倍以上，反映了它们在调节心率和心律中的特殊作用。β1亚型在两个区域均占主导。然而，β2亚型在窦房结中的丰度比心房心肌高2.5倍以上。人类窦房结中相对较高的β2受体密度与将该受体牵涉到调节心脏变时性的生理学研究一致。
