The molecular physiology of the cardiac transient outward potassium current (Ito) in normal and diseased myocardium

Gavin Y. Oudit, Zamaneh Kassiri, Rajan Sah, Rafael J. Ramirez, Carsten Zobel, Peter H. Backx

Research output: Contribution to journalArticlepeer-review

159 Scopus citations

Abstract

The Ca2+-independent transient outward potassium current (Ito) plays an important role in early repolarization of the cardiac action potential. Itohas been clearly demonstrated in myocytes from different cardiac regions and species. Two kinetic variants of cardiac Itohave been identified: fast Ito, called Ito.f, and slow Ito, called Ito.s. Recent findings suggest that Ito.fis formed by assembly of Kv4.2and/or Kv4.3alpha poreforming voltage-gated subunits while Ito.sis comprised of Kv1.4and possibly Kv1.7subunits. In addition, several regulatory subunits and pathways modulating the level and biophysical properties of cardiac Itohave been identified. Experimental findings and data from computer modeling of cardiac action potentials have conclusively established an important physiological role of Itoin rodents, with its role in large mammals being less well defined due to complex interplay between a multitude of cardiac ionic currents. A central and consistent electrophysiological change in cardiac disease is the reduction in Itodensity with a loss of heterogeneity of Itoexpression and associated action potential prolongation. Alterations of Itoin rodent cardiac disease have been linked to repolarization abnormalities and alterations in intracellular Ca2+homeostasis, while in larger mammals the link with functional changes is far less certain. We review the current literature on the molecular basis for cardiac Itoand the functional consequences of changes in Itothat occur in cardiovascular disease.

Original languageEnglish
Pages (from-to)851-872
Number of pages22
JournalJournal of Molecular and Cellular Cardiology
Volume33
Issue number5
DOIs
StatePublished - 2001

Keywords

  • Arrhythmia
  • Cardiac action potential
  • Congestive heart failure
  • Hypertrophy
  • Intracellular Ca
  • Myocytes
  • Regulatory subunits
  • Transient outward potassium current

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