Pathophysiological Role of K2P Channels in Human Diseases

Cell Physiol Biochem. 2021 Mar 6;55(S3):65-86. doi: 10.33594/000000338.

Abstract

The family of two-pore domain potassium (K2P) channels is critically involved in central cellular functions such as ion homeostasis, cell development, and excitability. K2P channels are widely expressed in different human cell types and organs. It is therefore not surprising that aberrant expression and function of K2P channels are related to a spectrum of human diseases, including cancer, autoimmune, CNS, cardiovascular, and urinary tract disorders. Despite homologies in structure, expression, and stimulus, the functional diversity of K2P channels leads to heterogeneous influences on human diseases. The role of individual K2P channels in different disorders depends on expression patterns and modulation in cellular functions. However, an imbalance of potassium homeostasis and action potentials contributes to most disease pathologies. In this review, we provide an overview of current knowledge on the role of K2P channels in human diseases. We look at altered channel expression and function, the potential underlying molecular mechanisms, and prospective research directions in the field of K2P channels.

Keywords: K2p channels; Pathophysiological mechanisms; Oncology; CNS disorders; Autoimmune diseases; Cardiovascular diseases; Hematologic diseases; Type 2 diabetes; Urinary and GI disorders.

Publication types

  • Review

MeSH terms

  • Action Potentials / physiology
  • Autoimmune Diseases / genetics
  • Autoimmune Diseases / metabolism*
  • Autoimmune Diseases / pathology
  • Cardiovascular Diseases / genetics
  • Cardiovascular Diseases / metabolism*
  • Cardiovascular Diseases / pathology
  • Gastrointestinal Diseases / genetics
  • Gastrointestinal Diseases / metabolism*
  • Gastrointestinal Diseases / pathology
  • Gene Expression
  • Hematologic Diseases / genetics
  • Hematologic Diseases / metabolism*
  • Hematologic Diseases / pathology
  • Homeostasis / genetics
  • Humans
  • Ion Transport
  • Neoplasms / genetics
  • Neoplasms / metabolism*
  • Neoplasms / pathology
  • Neurodegenerative Diseases / genetics
  • Neurodegenerative Diseases / metabolism*
  • Neurodegenerative Diseases / pathology
  • Organ Specificity
  • Potassium / metabolism
  • Potassium Channels, Tandem Pore Domain / classification
  • Potassium Channels, Tandem Pore Domain / genetics
  • Potassium Channels, Tandem Pore Domain / metabolism*
  • Protein Isoforms / classification
  • Protein Isoforms / genetics
  • Protein Isoforms / metabolism
  • Urologic Diseases / genetics
  • Urologic Diseases / metabolism*
  • Urologic Diseases / pathology

Substances

  • Potassium Channels, Tandem Pore Domain
  • Protein Isoforms
  • Potassium