Mechanisms and Alterations of Cardiac Ion Channels Leading to Disease: Role of Ankyrin-B in Cardiac Function

• Main Authors: Holly C. Sucharski, Emma K. Dudley, Caullin B. R. Keith, Mona El Refaey, Sara N. Koenig, Peter J. Mohler
• Format: Article
• Language: English
• Published: MDPI AG 2020-01-01
• Series: Biomolecules
• Subjects: ankyrin-b; <i>ank2</i>; ion channels; cardiovascular disease
• Online Access: https://www.mdpi.com/2218-273X/10/2/211

Ankyrin-B (encoded by <i>ANK2</i>), originally identified as a key cytoskeletal-associated protein in the brain, is highly expressed in the heart and plays critical roles in cardiac physiology and cell biology. In the heart, ankyrin-B plays key roles in the targeting and localization of key ion channels and transporters, structural proteins, and signaling molecules. The role of ankyrin-B in normal cardiac function is illustrated in animal models lacking ankyrin-B expression, which display significant electrical and structural phenotypes and life-threatening arrhythmias. Further, ankyrin-B dysfunction has been associated with cardiac phenotypes in humans (now referred to as &#8220;ankyrin-B syndrome&#8221;) including sinus node dysfunction, heart rate variability, atrial fibrillation, conduction block, arrhythmogenic cardiomyopathy, structural remodeling, and sudden cardiac death. Here, we review the diverse roles of ankyrin-B in the vertebrate heart with a significant focus on ankyrin-B-linked cell- and molecular-pathways and disease.