Specific decreasing of Na channel expression on the lateral membrane of cardiomyocytes causes fatal arrhythmias in Brugada syndrome.

Reduced cardiac sodium (Na) channel current (I) resulting from the loss-of-function of Na channel is a major cause of lethal arrhythmias in Brugada syndrome (BrS). Inspired by previous experimental studies which showed that in heart diseases I was reduced along with expression changes in Na channel within myocytes, we hypothesized that the local decrease in I caused by the alteration in Na channel expression in myocytes leads to the occurrence of phase-2 reentry, the major triggering mechanism of lethal arrhythmias in BrS. We constructed in silico human ventricular myocardial strand and ring models, and examined whether the Na channel expression changes in each myocyte cause the phase-2 reentry in BrS.

Systematic expression analysis of genes related to generation of action potentials in human iPS cell-derived cardiomyocytes.

Human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) are a valuable tool to characterize the pharmacology and toxic effects of drugs on heart cells. In particular, hiPSC-CMs can be used to identify drugs that generate arrhythmias. However, it is unclear whether the expression of genes related to generation of CM action potentials differs between hiPSC-CM cell lines and the mature human heart.

Integrative and theoretical research on the architecture of a biological system and its disorder.

An organism stems from assemblies of a variety of cells and proteins. This complex system serves as a unit, and it exhibits highly sophisticated functions in response to exogenous stimuli that change over time. The complete sequencing of the entire human genome has allowed researchers to address the enigmas of life and disease at the gene- or molecular-based level.

Mutant KCNJ3 and KCNJ5 Potassium Channels as Novel Molecular Targets in Bradyarrhythmias and Atrial Fibrillation.

Background: Bradyarrhythmia is a common clinical manifestation. Although the majority of cases are acquired, genetic analysis of families with bradyarrhythmia has identified a growing number of causative gene mutations. Because the only ultimate treatment for symptomatic bradyarrhythmia has been invasive surgical implantation of a pacemaker, the discovery of novel therapeutic molecular targets is necessary to improve prognosis and quality of life.