Two membrane levels of early afterdepolarization in sheep Purkinje fibers and their possible ionic mechanisms

Sheep Purkinje fibers were used to investigate early afterdepolarization (EAD) generation and its possible ionic mechanisms with bielectrode voltage clamp technique. Under low K+ (2.5 mmol/L K+) superfusion, two levels (-25 and -55 mV) of EAD could be induced on the background of automaticity. The bursts in low membrane level EAD were abolished by nifedipine (2.0 ??mol/L) whereas those in high membrane level were abolished by lidocaine (10 ??mol/L) and low temperature (30 ??C). The quasi-steady-state I-V relationship of the background currents obtained with step and ramp voltage clamp showed a negative phase in outward part of the rectification under 5.0 mmol/L K+ superfusion, while an inward current phase appeared between -55 and -25 mV level in the curve under 2.5 K+ treatment. Under the condition of EAD generation, the low and high membrane level (-25 and -55 mV) of voltage were clamped during the repolarization phase of action potential. On low membrane level of -25 mV, a slow inward current similar to ISi occurred followed by a slight outward current like Ik, whereas on high level of -55 mV, a continued inward current looked like If occurred. It was suggested that the two levels of plateau were based on the two zero current point in I-V curve under 2.5 mmol/L K+ superfusion, whereas bursts were based on the ISi, mainly ICa, for the low membrane level and If (and slow inactivated INa) for the high one.EI04517-5243