|Authors||J. Koivumäki, L. Skibsbye, M. Maleckar and T. Jespersen|
|Title||Action Potential Repolarisation in Healthy and Fibrillating Human Atria: Contribution of Small Conductance Calcium-Activated Potassium Channels|
|Afilliation||Scientific Computing, , Scientific Computing|
|Project(s)||Center for Biomedical Computing (SFF)|
|Publication Type||Talks, contributed|
|Year of Publication||2014|
|Location of Talk||Conference of the Scandinavian Physiological Society|
Aim: Recent studies have shown that small conductance calcium-activated potassium (SK) channels are expressed in human atria and have a functional role. The aim of this study was to further elucidate the role of SK channels in action potential (AP) repolarisation in human atrial cells. Methods and Results: Conductance and kinetics of SK channels, underlying the IKCa current, were adjusted in silico to replicate the contribution of the current to AP repolarisation ex vivo. Simulations were carried out in both healthy and chronic atrial fibrillation (AF) scenarios, based on our recently developed in silico human atrial cell model of chronic AF. Results show that in a healthy cell SK channel block increases APD90 \~20% and depolarises the resting membrane potential by \~2 mV. Furthermore, simulation results also suggest that the reduced contribution of SK channels to AP repolarisation in chronic AF is due to mainly attenuated Ca2+ dynamics and to a lesser extent to reduced expression of the channels. Conclusions: We conclude that model can recapitulate the basic features of IKCa, in that the SK channel block results in increased AP duration and depolarised resting membrane potential. This computational approach is potentially important for future studies aiming to understand the frequency-dependent Ca2+ modulation of IKCa as a contributor to both trigger and substrate of AF.