Ankyrin-B and ankyrin-G are co-expressed in cardiomyocytes but do not display overlapping localizations or functions. Humans heterozygous for mutations in Ank2 (ankyrin-B) display cardiac arrthymia and sudden death. Cardiomyocytes derived from ankyrin-B +/- mice have abnormal localization of IP3-receptor, sodium calcium exchanger (NCX), and Na+/K+ ATPase which can be rescued by the transfection of ankyrin-B but not ankyrin-G. The regulatory domain of ankyrin-B is responsible for driving ankyrin-B specific function in cardiomyocytes. We provide preliminary evidence identifying essential residues in the divergent ankyrin-B regulatory domain required for association with the membrane-binding domain and show that this association is required for ankyrin-B function in cardiomyocytes. We present three specific aims to: 1. Evaluate if the regulatory domain acts as a represser to interactions occurring at the membrane-binding domain. 2. Determine if the interdomain interaction is intramolecular or intermolecular. 3. Determine the intracellular compartment of mis-targeted IP3-receptor in cardiomyocytes transfected with an ankyrin-B construct harboring a mutation causing loss of interdomain interaction. [unreadable] [unreadable]