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

Biomolecules. 2020 Jan 31;10(2):211. doi: 10.3390/biom10020211.

Abstract

Ankyrin-B (encoded by ANK2), 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 "ankyrin-B syndrome") 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.

Keywords: ANK2; ankyrin-B; cardiovascular disease; ion channels.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Ankyrins / genetics*
  • Ankyrins / physiology*
  • Arrhythmias, Cardiac / metabolism*
  • Cardiovascular Diseases / metabolism*
  • Cytoskeleton / metabolism
  • Genetic Variation
  • Heart Block
  • Heart Rate
  • Humans
  • Ion Channels
  • Phenotype
  • Protein Domains
  • Protein Isoforms
  • Signal Transduction

Substances

  • ANK2 protein, human
  • Ankyrins
  • Ion Channels
  • Protein Isoforms