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

Xiao Ke Liu, Satsuki Yamada, Garvan M Kane, Alexey E. Alekseev, Denice M. Hodgson, Fearghas O'Cochlain, Arshad Jahangir, Takashi Miki, Susumu Seino, Andre Terzic

Research output: Contribution to journalArticle

62 Citations (Scopus)

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.

Original languageEnglish (US)
JournalDiabetes
Volume53
Issue numberSUPPL. 3
DOIs
StatePublished - Dec 2004

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KATP Channels
Catecholamines
Adenosine Triphosphate
Action Potentials
Cardiac Arrhythmias
Myocardium
Membranes

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism

Cite this

Genetic disruption of Kir6.2, the pore-forming subunit of ATP-sensitive K+ channel, predisposes to catecholamine-induced ventricular dysrhythmia. / Liu, Xiao Ke; Yamada, Satsuki; Kane, Garvan M; Alekseev, Alexey E.; Hodgson, Denice M.; O'Cochlain, Fearghas; Jahangir, Arshad; Miki, Takashi; Seino, Susumu; Terzic, Andre.

In: Diabetes, Vol. 53, No. SUPPL. 3, 12.2004.

Research output: Contribution to journalArticle

Liu, Xiao Ke ; Yamada, Satsuki ; Kane, Garvan M ; Alekseev, Alexey E. ; Hodgson, Denice M. ; O'Cochlain, Fearghas ; Jahangir, Arshad ; Miki, Takashi ; Seino, Susumu ; Terzic, Andre. / Genetic disruption of Kir6.2, the pore-forming subunit of ATP-sensitive K+ channel, predisposes to catecholamine-induced ventricular dysrhythmia. In: Diabetes. 2004 ; Vol. 53, No. SUPPL. 3.
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AU - O'Cochlain, Fearghas

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