抄録
IK1 is known to be responsible for the late rapid repolarization phase of action potential in cardiac ventricular myocytes, yet its role in the slow repolarization phase remains unclear. The amplitude of IK1 is determined by voltage-dependent block of the channel by internal spermine (SPM) and Mg2+. During repolarization, the release from the Mg2+ block in the presence of SPM induces a significant transient component of IK1 in voltage-clamp experiments. We developed a new model of the IK1 channel, which includes the high- and low-affinity modes of blocks by SPM and by Mg2+ (Yan & Ishihara, J. Physiol. 563, 2005), and examined the participation of this dynamic gating of IK1 channel to action potential repolarization by incorporating it into the Kyoto cardiac ventricular cell model. The model shows that the Mg2+-induced transient component of IK1 appears during the slow phase of repolarization. Thus, changes in the IK1 density significantly alter the action potential duration (APD), as has been demonstrated in experiments. A decrease in the Mg2+ concentration or an increase in the SPM concentration prolongs APD by reducing the transient component of IK1. Under this pathological condition, if the rapid component of delayed rectifier K+ current is blocked, APD is markedly prolonged. This model study predicts that the internal spermine and Mg2+ are important factors affecting the occurrence of early afterdepolarization and arrhythmia. [J Physiol Sci. 2006;56 Suppl:S72]
