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You searched for +publisher:"Washington University in St. Louis" +contributor:("Jianmin Cui, Vitaly Klyachko, George Van Hare, Richard Schuessler"). One record found.

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Washington University in St. Louis

1. Xu, Jiajing. KCNQ1/KCNE1 Interaction in the Cardiac IKs Channel and its Physiological Consequences.

Degree: PhD, Biomedical Engineering, 2018, Washington University in St. Louis

Dynamic conformational changes of ion channel proteins during activation gating determine their function as carriers of current. The relationship between these molecular movements and channel function over the physiological timescale of the action potential (AP) has not been fully established due to limitations of existing techniques. We constructed a library of possible cardiac IKs protein conformations and applied a combination of protein segmentation and energy linearization to study this relationship computationally. Simulations reproduced the effects of the beta-subunit (KCNE1) on the alpha-subunit (KCNQ1) dynamics and function, observed in experiments. Mechanistically, KCNE1 increased the probability of “visiting” conducting pore conformations on activation trajectories, thereby increasing IKs current. KCNE1 slowed IKs activation by impeding the voltage sensor (VS) movement and reducing its coupling to pore opening. Conformational changes along activation trajectories determined that the S4-S5 linker (S4S5L) plays an important role in these modulatory effects by KCNE1. Integration of these molecular structure-based IKs dynamics into a model of human cardiac ventricular myocyte, revealed that KCNQ1-KCNE1 interaction is essential for normal AP repolarization. Advisors/Committee Members: Yoram Rudy, Jianmin Cui, Vitaly Klyachko, George Van Hare, Richard Schuessler.

Subjects/Keywords: Cardiac action potential; Ion channels; Molecular simulation; Protein dynamics; Protein structure-function; Biomedical Engineering and Bioengineering; Chemistry; Molecular Biology; Other Chemistry

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6th Edition):

Xu, J. (2018). KCNQ1/KCNE1 Interaction in the Cardiac IKs Channel and its Physiological Consequences. (Doctoral Dissertation). Washington University in St. Louis. Retrieved from https://openscholarship.wustl.edu/eng_etds/388

Chicago Manual of Style (16th Edition):

Xu, Jiajing. “KCNQ1/KCNE1 Interaction in the Cardiac IKs Channel and its Physiological Consequences.” 2018. Doctoral Dissertation, Washington University in St. Louis. Accessed August 10, 2020. https://openscholarship.wustl.edu/eng_etds/388.

MLA Handbook (7th Edition):

Xu, Jiajing. “KCNQ1/KCNE1 Interaction in the Cardiac IKs Channel and its Physiological Consequences.” 2018. Web. 10 Aug 2020.

Vancouver:

Xu J. KCNQ1/KCNE1 Interaction in the Cardiac IKs Channel and its Physiological Consequences. [Internet] [Doctoral dissertation]. Washington University in St. Louis; 2018. [cited 2020 Aug 10]. Available from: https://openscholarship.wustl.edu/eng_etds/388.

Council of Science Editors:

Xu J. KCNQ1/KCNE1 Interaction in the Cardiac IKs Channel and its Physiological Consequences. [Doctoral Dissertation]. Washington University in St. Louis; 2018. Available from: https://openscholarship.wustl.edu/eng_etds/388

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