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Allosteric Interaction of Rapid Delayed Rectifier Protein and Its Role in Cardiac Repolarization

Biomedical Sciences Research Institute Computer Science Research Institute Environmental Sciences Research Institute Nanotechnology & Advanced Materials Research Institute

Wang, C, Beyerlein, P, Hammer, P, Krause, A, Nugent, C and Dubitzky, Werner (2008) Allosteric Interaction of Rapid Delayed Rectifier Protein and Its Role in Cardiac Repolarization. In: COMPUTERS IN CARDIOLOGY 2008, VOLS 1 AND 2, Bologna, Italy. UNSPECIFIED. 4 pp. [Conference contribution]

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URL: http://www.cinc.org/archives/2008/pdf/0589.pdf

Abstract

The alpha-subunit of the rapid delayed rectifier I-kr has been identified to be composed of multiple function domains. However, much less is known about the electrophysiological consequences of the interaction properties in the assembled channel protein. In this paper we present a detailed conformational kinetic model through characterizing allosteric interactions between the voltage sensing domain and the cytoplasmic activation gate. The correlation of kinetic properties to action potential (AP) dynamics was investigated at different basic cycle lengths. We found that in response to driving forces ranging from -40 m V to 60 mV two open states were populated. A significant elevation of I-kr at the early AP was attributable to an available reserve and the open-state accumulation, leading to shortening of AP duration at rapid rates. In contrast, the development of a dominant late peak Ikr with a steep slope morphology observed at slow rates arose from the allosteric coupled activation pathway. The existence of available reserve suggests Ikr has a repolarization reserve which facilitates its rate adaptation.

Item Type:Conference contribution (Paper)
Faculties and Schools:Faculty of Life and Health Sciences
Faculty of Life and Health Sciences > School of Biomedical Sciences
Research Institutes and Groups:Biomedical Sciences Research Institute
Biomedical Sciences Research Institute > Molecular Medicine
Biomedical Sciences Research Institute > Molecular Medicine > Nano Systems Biology
ID Code:4445
Deposited By:Professor Werner Dubitzky
Deposited On:05 Jan 2010 15:32
Last Modified:24 Jun 2011 14:56

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