Published Online
on August 29, 2005

A more recent version of this article appeared on September 6, 2005

This Article Full Text (PDF) Data Supplement Clinical Perspective Correction (v120,pe84) All Versions of this Article: 112/10/1384    most recent CIRCULATIONAHA.105.543306v1 Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Silva, J. Articles by Rudy, Y. Search for Related Content PubMed PubMed Citation Articles by Silva, J. Articles by Rudy, Y. Related Collections Electrophysiology Gene expression Ion channels/membrane transport Related Article

Submitted on February 17, 2005
Revised on April 22, 2005
Accepted on May 10, 2005

Subunit Interaction Determines I_Ks Participation in Cardiac Repolarization and Repolarization Reserve

Jonathan Silva MS and Yoram Rudy PhD^*

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

^* To whom correspondence should be addressed. E-mail: rudy{at}wustl.edu.

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 -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. [Extract] [Full Text]

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