No abstract

Na + -Ca 2+ exchange (NCX) current has been suggested to play a role in cardiac pacemaking, particularly in association with Ca 2+ release from the sarcoplasmic reticulum (SR) that occurs just before the action potential upstroke. The present experiments explore in more detail the contribution of NCX to pacemaking. Na + -Ca 2+ exchange current was inhibited by rapid switch to low-Na + solution (with Li + replacing Na + ) within the time course of a single cardiac cycle to avoid slow secondary effects. Rapid switch to low-Na + solution caused immediate cessation of spontaneous action potentials. ZD7288 (3 μM), to block I f (funny current) channels, slowed but did not stop the spontaneous activity, and tetrodotoxin (10 μM), to block Na + channels, had little effect, but in the presence of either of these agents, rapid switch to low-Na + solution again caused immediate cessation of spontaneous action potentials. Spontaneous electrical activity was also stopped following loading of the cells with the Ca 2+ chelators BAPTA and EGTA, and by exposure to the NCX inhibitor KB-R7943 (5 μM). When rapid switch to low-Na + solution caused cessation of spontaneous activity, this was found (using confocal microscopy, with fluo-4 as the

No abstract