Genetic disruption of Kir6.2, the pore-forming subunit of ATP-sensitive K+ channel, predisposes to catecholamine-induced ventricular dysrhythmia.
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.
Liu
Xiao-Ke
XK
Division of Cardiovascular Diseases, Department of Medicine, Mayo Clinic, Rochester, MN 55905, USA.
Yamada
Satsuki
S
Kane
Garvan C
GC
Alekseev
Alexey E
AE
Hodgson
Denice M
DM
O'Cochlain
Fearghas
F
Jahangir
Arshad
A
Miki
Takashi
T
Seino
Susumu
S
Terzic
Andre
A
D000255:Adenosine Triphosphate / Q000502:physiology; D000818:Animals; D002395:Catecholamines / Q000633:toxicity*; D017353:Gene Deletion; D051379:Mice; D018345:Mice, Knockout; D024661:Potassium Channels, Inwardly Rectifying / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D021122:Protein Subunits / Q000172:deficiency / Q000235:genetics / Q000502:physiology; D014693:Ventricular Fibrillation / Q000139:chemically induced / Q000235:genetics*; D000099161:Kcnj11 Channel
D000255:Adenosine Triphosphate; D002395:Catecholamines; D024661:Potassium Channels, Inwardly Rectifying; D021122:Protein Subunits; D000099161:Kcnj11 Channel