Relative Densities of Muscarinic Cholinergic and β-Adrenergic Receptors in the Canine Sinoatrial Node and Their Relation to Sites of Pacemaker Activity

Abstract

Abstract The site of earliest extracellular electrical activation in the sinoatrial node (SAN) is known to shift in response to autonomic stimuli, but the mechanisms underlying this phenomenon and the determinants of the location of dominant pacemaker activity have not been elucidated. The present study was designed to characterize the spatial distribution of muscarinic cholinergic and β-adrenergic receptors in the canine SAN and to determine whether a consistent relationship exists between autonomic receptor densities and the site of dominant pacemaker activity. We used quantitative light-microscopic autoradiography of radioligand binding sites to characterize the spatial distribution of muscarinic cholinergic and β-adrenergic receptor subtypes in tissue sections containing the SAN and adjacent right atrial muscle from 18 canine hearts. Muscarinic receptor density was 5.4 times greater in SAN cells than in atrial myocytes ( P <.01). Total β-adrenergic receptor density was more than 3 times greater in SAN cells than in atrial myocytes ( P <.0001), due entirely to the significantly greater number of β 1 -adrenergic receptors in the SAN. The region of dominant pacemaker activity, localized in 4 hearts with in vitro mapping, consistently exhibited greater densities of muscarinic and β 1 -adrenergic receptors than other SAN regions. Muscarinic receptor density in the dominant pacemaker region was 18±2% and 29±7% higher than in adjacent superior and inferior regions, respectively. β 1 -Receptor density in the dominant site was 53±5% and 26±4% higher than in adjacent superior and inferior SAN regions, respectively. Thus, the SAN is richly endowed with both muscarinic cholinergic and β 1 -adrenergic receptors. Differential responsiveness to autonomic inputs, related perhaps to regional differences in receptor density, may help determine the spatial localization of pacemaker activity.