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(Circulation. 2005;112:1384-1391.)
© 2005 American Heart Association, Inc.

Arrhythmia/Electrophysiology

Subunit Interaction Determines I_Ks Participation in Cardiac Repolarization and Repolarization Reserve

Jonathan Silva, MS; Yoram Rudy, PhD

From the Cardiac Bioelectricity and Arrhythmia Center, Washington University in St Louis, St Louis, Mo.

Correspondence to Yoram Rudy, PhD, Campus Box 1097, Whitaker Hall, Room 290, Washington University in St Louis, One Brookings Dr, St Louis, MO 63130-4899. E-mail rudy{at}wustl.edu

Received February 17, 2005; revision received April 22, 2005; accepted May 10, 2005.

Background— The role of I_Ks, the slow delayed rectifier K⁺ current, in cardiac ventricular repolarization has been a subject of debate.

Methods and Results— We develop a detailed Markov model of I_Ks and its -subunit KCNQ1 and examine their kinetic properties during the cardiac ventricular action potential at different rates. We observe that interaction between KCNQ1 and KCNE1 (the ß-subunit) confers kinetic properties on I_Ks that make it suitable for participation in action potential repolarization and its adaptation to rate changes; in particular, the channel develops an available reserve of closed states near the open state that can open rapidly on demand.

Conclusions— Because of its ability to form an available reserve, I_Ks can function as a repolarization reserve when I_Kr, the rapid delayed rectifier, is reduced by disease or drug and can prevent excessive action potential prolongation and development of arrhythmogenic early afterdepolarizations.

Key Words: action potentials • electrophysiology • ion channels

Related Article:

Protecting the Heart Against Arrhythmias: Potassium Current Physiology and Repolarization Reserve

Dan M. Roden and Tao Yang
Circulation 2005 112: 1376-1378. [Full Text]

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