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

C Wang, P Beyerlein, P Hammer, A Krause, C Nugent, Werner Dubitzky

Research output: Chapter in Book/Report/Conference proceedingConference contribution

1 Citation (Scopus)

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.
LanguageEnglish
Title of host publicationUnknown Host Publication
Place of Publication345 E 47TH ST, NEW YORK, NY 10017 USA
Pages589-592
Number of pages4
Publication statusPublished - 2008
EventCOMPUTERS IN CARDIOLOGY 2008, VOLS 1 AND 2 - Bologna, Italy
Duration: 1 Jan 2008 → …

Conference

ConferenceCOMPUTERS IN CARDIOLOGY 2008, VOLS 1 AND 2
Period1/01/08 → …

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protein
kinetics
rate

Cite this

Wang, C., Beyerlein, P., Hammer, P., Krause, A., Nugent, C., & Dubitzky, W. (2008). Allosteric Interaction of Rapid Delayed Rectifier Protein and Its Role in Cardiac Repolarization. In Unknown Host Publication (pp. 589-592). 345 E 47TH ST, NEW YORK, NY 10017 USA.
Wang, C ; Beyerlein, P ; Hammer, P ; Krause, A ; Nugent, C ; Dubitzky, Werner. / Allosteric Interaction of Rapid Delayed Rectifier Protein and Its Role in Cardiac Repolarization. Unknown Host Publication. 345 E 47TH ST, NEW YORK, NY 10017 USA, 2008. pp. 589-592
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title = "Allosteric Interaction of Rapid Delayed Rectifier Protein and Its Role in Cardiac Repolarization",
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.",
author = "C Wang and P Beyerlein and P Hammer and A Krause and C Nugent and Werner Dubitzky",
note = "35th Annual Conference on Computers in Cardiology, Bologna, ITALY, SEP 14-17, 2008",
year = "2008",
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Wang, C, Beyerlein, P, Hammer, P, Krause, A, Nugent, C & Dubitzky, W 2008, Allosteric Interaction of Rapid Delayed Rectifier Protein and Its Role in Cardiac Repolarization. in Unknown Host Publication. 345 E 47TH ST, NEW YORK, NY 10017 USA, pp. 589-592, COMPUTERS IN CARDIOLOGY 2008, VOLS 1 AND 2, 1/01/08.

Allosteric Interaction of Rapid Delayed Rectifier Protein and Its Role in Cardiac Repolarization. / Wang, C; Beyerlein, P; Hammer, P; Krause, A; Nugent, C; Dubitzky, Werner.

Unknown Host Publication. 345 E 47TH ST, NEW YORK, NY 10017 USA, 2008. p. 589-592.

Research output: Chapter in Book/Report/Conference proceedingConference contribution

TY - GEN

T1 - Allosteric Interaction of Rapid Delayed Rectifier Protein and Its Role in Cardiac Repolarization

AU - Wang, C

AU - Beyerlein, P

AU - Hammer, P

AU - Krause, A

AU - Nugent, C

AU - Dubitzky, Werner

N1 - 35th Annual Conference on Computers in Cardiology, Bologna, ITALY, SEP 14-17, 2008

PY - 2008

Y1 - 2008

N2 - 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.

AB - 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.

M3 - Conference contribution

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EP - 592

BT - Unknown Host Publication

CY - 345 E 47TH ST, NEW YORK, NY 10017 USA

ER -

Wang C, Beyerlein P, Hammer P, Krause A, Nugent C, Dubitzky W. Allosteric Interaction of Rapid Delayed Rectifier Protein and Its Role in Cardiac Repolarization. In Unknown Host Publication. 345 E 47TH ST, NEW YORK, NY 10017 USA. 2008. p. 589-592