Role of the transient outward potassium current in the genesis of early afterdepolarizations in cardiac cells Full Text
Cardiovascular Research, 08/03/2012
Exclusive author commentary
Zhao Z et al. – In cardiac cells, Ito, with a proper conductance and inactivation speed, potentiates early afterdepolarizations (EADs) by setting the action potential plateau into the voltage range where ICa,L reactivation is facilitated and IKs activation is slowed.
Lai-Hua Xie (08/03/2012) comments:
QT prolongation has been used clinically as a risk marker for cardiac arrhythmias leading to sudden cardiac death. The main mechanism is that prolongation of action potential duration (APD) or reduced repolarization reserve facilitates early afterdepolarization (EAD) generation. However, it is also known that lengthening APD may not necessarily lead to the genesis of EADs and arrhythmias. Our current study is set to investigate, besides the prolongation of APD, the additional criterion that may exist to better predict the EAD genesis and thus the risk of arrhythmias. We used an integrative approach by combining experiments and computer simulations to study the effects of the transient outward potassium current (Ito) on EAD genesis under the condition of reduced repolarization reserve. We show that although Ito is an outward current, it speeds repolarization of the early phase (phase-1) of the action potential to the voltage range where the L-type calcium channel (ICa,L) is available for reactivation and the delayed rectifier potassium current (IKs) is slower, generating a favorable condition for EAD formation. Our study extends the current concept of reduced repolarization reserve and will add to the understanding for searching additional criterion of arrhythmia risk besides QT prolongation and better treatment of sudden cardiac death.
