The effects of pinacidil and acetylcholine (Ach) on action potential (AP) and early afterdepolarization (EAD) were investigated in mouse atrial fibers. Under treatment with pinacidil the AP and EAD were affected only with the concentration of 8 x 10(-5) M, which inhibited EAD but did not affect AP except for only a minor reduction of action potential duration (APD). After withdrawal of pinacidil, the inhibitory effect of EAD was enhanced. Under treatment with Ach (2 x 10(-7) M), AP was not changed except the APD, which was significantly reduced, and the EAD was completely abolished. Withdrawal of Ach produced a rebound increase in APD and led to induction of EAD or promoted EAD to more extensive level such as appearance of long second plateau. Atropine (1 x 10(-7) M) abolished the rebound effect caused by withdrawal of Ach. The mechanism of EAD generation induced by removing Ach is discussed.