|Authors||I. G. M. van Herck|
|Title||Biophysical and pharmacological properties of small conductance calcium-activated potassium channels|
|Project(s)||Department of Computational Physiology, AFib-TrainNet: EU Training Network on Novel Targets and Methods in Atrial Fibrillation|
|Publication Type||PhD Thesis|
|Year of Publication||2021|
|Degree awarding institution||University of Oslo|
|Other Numbers||ISSN 1501-7710|
The small conductance calcium-activated potassium (SK) channel contributes to atrial repolarization and has an implicated role in onset and progression of atrial fibrillation (AF). This suggests SK channels as a promising target in AF treatment, but the effect of SK modulation on human electrophysiology is complex and knowledge is limited.
Physiological experiments are limited by technical and ethical boundaries, and are therefore insufficient in bridging the gap across scales and translation to humans. Instead, an integrated approach of patch clamp experiments and biophysical modeling is required to unravel the complexity and potential of SK channel pharmacology in AF treatment.
This dissertation covers aspects from patch clamp experiments of a channel or population and the consecutive development of computational Markov models. These models describe biophysical and pharmacological properties of SK channels in detail. They thus enable further myocyte and tissue level simulations, assessing the impact of SK channels on human atrial electrophysiology and arrhythmogenesis.