Genetic disruption of Kir6.2, the pore-forming subunit of ATP-sensitive K+ channel, predisposes to catecholamine-induced ventricular dysrhythmia

Diabetes. 2004 Dec:53 Suppl 3:S165-8. doi: 10.2337/diabetes.53.suppl_3.s165.

Abstract

Metabolic-sensing ATP-sensitive K+ channels (KATP channels) adjust membrane excitability to match cellular energetic demand. In the heart, KATP channel activity has been linked to homeostatic shortening of the action potential under stress, yet the requirement of channel function in securing cardiac electrical stability is only partially understood. Here, upon catecholamine challenge, disruption of KATP channels, by genetic deletion of the pore-forming Kir6.2 subunit, produced defective cardiac action potential shortening, predisposing the myocardium to early afterdepolarizations. This deficit in repolarization reserve, demonstrated in Kir6.2-knockout hearts, translated into a high risk for induction of triggered activity and ventricular dysrhythmia. Thus, intact KATP channel function is mandatory for adequate repolarization under sympathetic stress providing electrical tolerance against triggered arrhythmia.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adenosine Triphosphate / physiology
  • Animals
  • Catecholamines / toxicity*
  • Gene Deletion*
  • Mice
  • Mice, Knockout
  • Potassium Channels, Inwardly Rectifying / deficiency
  • Potassium Channels, Inwardly Rectifying / genetics
  • Potassium Channels, Inwardly Rectifying / physiology*
  • Protein Subunits / deficiency
  • Protein Subunits / genetics
  • Protein Subunits / physiology
  • Ventricular Fibrillation / chemically induced
  • Ventricular Fibrillation / genetics*

Substances

  • Catecholamines
  • Kir6.2 channel
  • Potassium Channels, Inwardly Rectifying
  • Protein Subunits
  • Adenosine Triphosphate