Modelling the molecular basis of cardiac repolarization

To study the properties of ion-channel gating ( I_Ks , the slow delayed rectifier K ⁺ channel) that underlie the channel's participation in rate-dependent repolarization of the cardiac action potential (AP).

Computational biology approach was used to simulate the channel gating and the AP of a mammalian ventricular myocyte.

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.

I_Ks 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 I_Ks effective in providing repolarization reserve when other repolarizing currents are compromised by disease or drugs.