Download 2016 department of medicine research day

2016 DEPARTMENT OF MEDICINE RESEARCH DAY
Title of Poster: Arrhythmogenic effects of Ca-activated small conductance potassium
channel in failing myocytes
Presenter: Imesh Samarakoon
Division: Cardiology
☐Faculty ☐Fellow ☐Resident ☐Post-doc Research Fellow ☐Graduate Student ☐Medical Student ☒Other (Undergraduate)
Principal Investigator/Mentor: Zhilin Qu Co-Investigators: Michael Liu, Alan Garfinkel
Thematic Poster Category: Neurobiology, Smooth, Striated and Cardiac Muscle Function, Cardiac Conduction
Systems and Arrhythmias, Biology of Perception and Pain, Psychoneuroimmunology
Abstract
Arrhythmias, such as ventricular fibrillation (VF), are a major cause of sudden cardiac death (SCD) in
patients with heart failure (HF), yet the mechanisms by which it manifests are not well understood.
Recent experimental studies showed that small conductance calcium-activated potassium (SK)
channels are upregulated in HF, which tends to shorten action potential duration (APD) to protect the
heart from QT-prolongation related arrhythmias. This is demonstrated in experiments that the
administration of apamin to ventricles under slower pacing resulted in early afterdepolarizations
(EADs) and torsades de pointes (TdP). We seek to use computer modeling as a tool to investigate the
effects of SK channel on arrhythmogenic APD and calcium cycling dynamics in failing ventricular
myocytes. We developed a mathematical model of SK current and incorporated into two types of cell
models: a low-dimensional non-spatial cell model and a spatial cell model with a coupled network of
calcium release units. We show that increasing the SK current in both models shortens APD but
promoted alternans. The alternans tends to be electromechanically discordant, i.e., calcium alternates
out of phase with APD alternans. Moreover, the spatial distribution of the SK also plays important role
in the formation of alternans.