The effect of block of the L-type Ca2+ current by 2 microM nifedipine and of the Na+ current by 20 microM tetrodotoxin on the center (normally the leading pacemaker site) and periphery (latent pacemaker tissue) of the rabbit sinoatrial node was investigated. Spontaneous action potentials were recorded with microelectrodes from either an isolated right atrium containing the whole node or small balls of tissue (approximately 0.3-0.4 mm in diameter) from different regions of the node. Nifedipine abolished the action potential in the center, but not usually in the periphery, in both the intact sinoatrial node and the small balls. Tetrodotoxin had no effect, on electrical activity in small balls from the center, but it decreased the takeoff potential and upstroke velocity and slowed the spontaneous activity (by 49 +/- 10%; n = 11) in small balls from the periphery. It is concluded that whereas the L-type Ca2- current plays an obligatory role in pacemaking in the center, the Na+ current plays a major role in pacemaking in the periphery.

Regional differences in electrical activity in rabbit sinoatrial node have been investigated by recording action potentials throughout the intact node or from small balls of tissue from different regions. In the intact node, action potential duration was greatest at or close to the leading pacemaker and declined markedly in all directions from it, e.g., by 74 ± 4% (mean ± SE, n = 4) to the crista terminalis. Similar data were obtained from the small balls. The gradient is down the conduction pathway and will help prevent reentry. In the intact node, a zone of inexcitable tissue with small depolarizations of <25 mV or stable resting potentials was discovered in the inferior part of the node, and this will again help prevent reentry. The intrinsic pacemaker activity of the small balls was slower in tissue from more inferior (as well as more central) parts of the node [e.g., cycle length increased from 339 ± 13 ms ( n = 6) to 483 ± 13 ms ( n = 6) in transitional tissue from more superior and inferior sites], and this may help explain pacemaker shift.

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.

Mouse SAN and AVN showed distinct different response to the inhibition of RyR, TTX-sensitive INa, IKr and iKur, which reflects the variation in contribution of these currents to the pacemaker function of the cardiac nodes in the mouse. Our data provide valuable information for developing virtual tissue models of mouse SAN and AVN.

Effects of block of the rapid delayed rectifier K+current ( I K,r) by E-4031 on the electrical activity of small ball-like tissue preparations from different regions of the rabbit sinoatrial node were measured. The effects of partial block of I K,r by 0.1 μM E-4031 varied in different regions of the node. In tissue from the center of the node spontaneous activity was generally abolished, whereas in tissue from the periphery spontaneous activity persisted, although the action potential was prolonged, the maximum diastolic potential was decreased, and the spontaneous activity slowed. After partial block of I K,r, the electrical activity of peripheral tissue was more like that of central tissue under normal conditions. One possible explanation of these findings is that the density of I K,r is greater in the periphery of the node; this would explain the greater resistance of peripheral tissue to I K,r block and help explain why, under normal conditions, the maximum diastolic potential is more negative, the action potential is shorter, and pacemaking is faster in the periphery.