Referenced in: none

Automatically associated channels: Kv10.1 , Slo1

Title: A novel genetic pathway for sudden cardiac death via defects in the transition between ventricular and conduction system cell lineages.

Authors: V T Nguyên-Trân, S W Kubalak, S Minamisawa, C Fiset, K C Wollert, A B Brown, P Ruiz-Lozano, S Barrere-Lemaire, R Kondo, L W Norman, R G Gourdie, M M Rahme, G K Feld, R B Clark, W R Giles, K R Chien

Journal, date & volume: Cell, 2000 Sep 1 , 102, 671-82

PubMed link: http://www.ncbi.nlm.nih.gov/pubmed/11007485

Abstract
HF-1 b, an SP1 -related transcription factor, is preferentially expressed in the cardiac conduction system and ventricular myocytes in the heart. Mice deficient for HF-1 b survive to term and exhibit normal cardiac structure and function but display sudden cardiac death and a complete penetrance of conduction system defects, including spontaneous ventricular tachycardia and a high incidence of AV block. Continuous electrocardiographic recordings clearly documented cardiac arrhythmogenesis as the cause of death. Single-cell analysis revealed an anatomic substrate for arrhythmogenesis, including a decrease and mislocalization of connexins and a marked increase in action potential heterogeneity. Two independent markers reveal defects in the formation of ventricular Purkinje fibers. These studies identify a novel genetic pathway for sudden cardiac death via defects in the transition between ventricular and conduction system cell lineages.