Modelling the molecular basis of cardiac repolarization
Cardiac Bioelectricity and Arrhythmia Center (CBAC), Washington University in St Louis, 290 Whitaker Hall, Campus Box 1097, One Brookings Drive, St Louis, MO 63130-4899, USA
Aims: To study the properties of ion-channel gating (IKs, the slow delayed rectifier K+ channel) that underlie the channel's participation in rate-dependent repolarization of the cardiac action potential (AP).
Methods: Computational biology approach was used to simulate the channel gating and the AP of a mammalian ventricular myocyte.
Results: At fast rate, channels accumulate at closed state near the open state, from which they can rapidly open to generate large repolarizing current late during the AP, effectively shortening its duration.
Conclusion: IKs builds an ‘available reserve’ of channels that can open ‘on-demand’ to repolarize the AP and shorten its duration at fast rate (‘rate-adaptation’). This property also makes IKs effective in providing repolarization reserve when other repolarizing currents are compromised by disease or drugs.
Key Words: Cardiac repolarization, Cardiac arrhythmias, Ion channels, Cardiac action potential
Corresponding author. Tel: +1 314 935 8160; fax: +1 314 935 8168. E-mail address: rudy{at}wustl.edu