Mouse models for studying pacemaker channel function and sinus node arrhythmia.

Pacemaker activity of the heart is generated by a small group of cells forming the sinoatrial node (SAN). Cells of the SAN are spontaneously active and generate action potentials with remarkable regularity and stability under all physiological conditions. The exact molecular mechanisms underlying pacemaker potentials in the SAN have not yet been fully elucidated.

Tamoxifen-inducible gene deletion in the cardiac conduction system.

Temporally controlled gene deletion provides a powerful technique for examination of gene function in vivo. To permit use of this technology in the study of cardiac pacemaking, we attempted to generate a mouse line expressing an inducible Cre recombinase selectively in cardiac pacemaker cells. The tamoxifen-inducible CreER(T2) construct was 'knocked in' into the pacemaker channel HCN4 locus.