Guiding Cardiac Conduction With GATA.

Abstract

Despite remarkable progress in the past few years, the gene regulatory networks underlying formation and function of the cardiac conduction system (CCS) remain incompletely understood. Transcription factors such as NXK2.5 and TBX2/3/5 that control various aspects of heart development have emerged as key regulators of cardiac conduction gene expression and function. By showing alterations in the structure of the atrioventricular node (AVN) and the electrophysiological parameters of mice harboring a mutated GATA-binding factor 6 (GATA6) protein, Liu et al1 add a new player to the growing list of transcription factors involved in cardiac rhythm regulation. This finding provides insight that will help advance efforts to elucidate the pathogenesis of cardiac rhythm disturbances. Article see p 284 In human, cardiac rhythm disturbances are a major cause of mortality and morbidity from fetal to adult life. They can develop in response to numerous conditions, such as electrolyte imbalance, cardiovascular disease including ischemia and pressure overload, structural heart malformations, or as undesirable drug side effects. Arrhythmias and conduction defects can also be because of inherited mutations in genes that affect generation or propagation of the electric impulse of the heart, as exemplified by the long QT Syndrome. How these genetic or acquired factors influence cardiac rhythm is not yet fully understood. In the past years, great strides were achieved for treatment of these important disorders from drug and ablation therapy to implantable devices. However, all treatments have significant short falls and none is curative. A better understanding of the molecular mechanism underlying normal development of the CCS will help unravel the pathogenesis of rhythm disturbances and the development of effective therapies. Proper heart contraction and relaxation processes are controlled by the CCS, a specialized component of the heart responsible for initiating and orchestrating the propagation of the electric signal required for optimal …