Regional differences in effects of E-4031 within the sinoatrial node

Abstract

Effects of block of the rapid delayed rectifier K+ current (IK,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 IK,r by 0.1 microM 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 IK,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 IK,r is greater in the periphery of the node; this would explain the greater resistance of peripheral tissue to IK,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.