title: Linking a genetic defect to its cellular phenotype in a cardiac arrhythmia.
abstract: Advances in genetics and molecular biology have provided an extensive body of information on the structure and function of the elementary building blocks of living systems. Genetic defects in membrane ion channels can disrupt the delicate balance of dynamic interactions between the ion channels and the cellular environment, leading to altered cell function. As ion-channel defects are typically studied in isolated expression systems, away from the cellular environment where they function physiologically, a connection between molecular findings and the physiology and pathophysiology of the cell is rarely established. Here we describe a single-channel-based Markovian modelling approach that bridges this gap. We achieve this by determining the cellular arrhythmogenic consequences of a mutation in the cardiac sodium channel that can lead to a clinical arrhythmogenic disorder (the long-QT syndrome) and sudden cardiac death.
authors.affiliation: Cardiac Bioelectricity Research and Training Center, Department of Physiology and Biophysics, Case Western Reserve University, Cleveland, Ohio 44106-7207, USA.
authors.forename: C E
authors.initials: CE
authors.lastname: Clancy
authors.forename: Y
authors.initials: Y
authors.lastname: Rudy
mesh_terms: D000200:Action Potentials; D006801:Humans; D015640:Ion Channel Gating; D008133:Long QT Syndrome / Q000235:genetics* / Q000378:metabolism; D008390:Markov Chains; D008955:Models, Cardiovascular; D008957:Models, Genetic; D009154:Mutation; D009206:Myocardium / Q000378:metabolism; D010641:Phenotype; D015222:Sodium Channels / Q000235:genetics* / Q000378:metabolism
chemical_list: D015222:Sodium Channels