Variation in effects of Cs+, UL-FS-49, and ZD-7288 within sinoatrial node

The effects of Cs+, UL-FS-49, and ZD-7288 on action potentials recorded from central, transitional, and peripheral sites in the rabbit sinoatrial (SA) node have been investigated. In isolated right atrial preparations, including the whole SA node, Cs+ (2 mM), UL-FS-49 (1 microM), and ZD-7288 (3 microM), decreased the spontaneous rate by 12 +/- 2% (n = 21), 16 +/- 3% (n = 10), and 13 +/- 3% (n = 10). They decreased the slope of the pacemaker potential without affecting action potential characteristics. The decrease of pacemaker slope was maximal (69-120%) in the periphery and minimal (22-25%) in the center. In experiments on small ball-like tissue specimens (approximately 0.3 mm diam), a decrease in spontaneous rate and pacemaker slope by Cs+ (2 mM) was largest (approximately 19 and approximately 47%) in tissue from the periphery and least (approximately 7 and approximately 17%) in tissue from the center. Because the hyperpolarization-activated inward current (If) is reduced by each of these agents, the results suggest that this current might play a relatively minor role in the center but a more important role in the periphery of the SA node.