Jonathan Silva1, Yoram Rudy. 1. Cardiac Bioelectricity and Arrhythmia Center, Washington University, St Louis, MO 63130-4899, USA.
Abstract
BACKGROUND: The role of IKs, 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 IKs and its alpha-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 beta-subunit) confers kinetic properties on IKs 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, IKs can function as a repolarization reserve when IKr, the rapid delayed rectifier, is reduced by disease or drug and can prevent excessive action potential prolongation and development of arrhythmogenic early afterdepolarizations.
BACKGROUND: The role of IKs, 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 IKs and its alpha-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 beta-subunit) confers kinetic properties on IKs 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, IKs can function as a repolarization reserve when IKr, the rapid delayed rectifier, is reduced by disease or drug and can prevent excessive action potential prolongation and development of arrhythmogenic early afterdepolarizations.
Authors: Olfat A Malak; Grigory S Gluhov; Anastasia V Grizel; Kseniya S Kudryashova; Olga S Sokolova; Gildas Loussouarn Journal: J Biol Chem Date: 2019-02-26 Impact factor: 5.157