As shown in dog atrial myocytes and patients with AF, the rate-induced Ca2+ overload is thought to activate calpain that cleaves cell proteins and leads to the breakdown of the IK,ACh inhibitory protein kinase C alpha.24,38 Together with increased membrane translocation of the stimulatory protein kinase C epsilon, these mechanisms are likely to contribute to IK,ACh remodelling in AF and TP models.38,57. The gene discussed is PRKCE; the disease is atrial fibrillation.