BETA-ADRENERGIC AND MUSCARINIC CHOLINERGIC RECEPTOR DENSITIES IN THE HUMAN SINOATRIAL NODE - IDENTIFICATION OF A HIGH BETA(2)-ADRENERGIC RECEPTOR DENSITY

The objective of this study was to measure autonomic receptor densitie s 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 c ompartments of the sinoatrial node and adjacent myocardium. Total beta -adrenergic receptors were measured with the nonsubtype selective radi oligand [I-125]iodocyanopindolol. beta(2)-Adrenergic receptors were de termined by measuring the amount of radioactivity bound to sections in cubated with radioligand in the presence of the highly beta(1)-selecti ve antagonist CGP-20712A. Specific autoradiographic grain densities we re normalized to myocyte area/unit tissue area. Myocytes in the sinoat rial node occupied 47.7% +/- 0.1% of the total tissue area compared wi th 92.8% +/- 0.1% in myocardium (P < 0.001). Total specific beta-adren ergic receptor density per unit myocyte area was 3.5 +/- 0.9 times gre ater in the sinoatrial node than in myocardium (P < 0.001). The relati ve 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 i n the sinoatrial node than in the atrium. Thus, total beta-adrenergic and muscarinic cholinergic receptor densities are > 3-fold higher in t he sinoatrial node than adjacent atrial myocardium, reflecting their s pecialized roles in regulating cardiac rate and rhythm. The beta(1)-su btype is predominant in both regions. The beta(2)-subtype, however, is > 2.5-fold more abundant in the sinoatrial node than in atrial myocar dium. The relatively high beta(2)-receptor density in the human sinoat rial node is consistent with physiologic studies that implicate this r eceptor in regulating cardiac chronotropism.