| Cardiac channelopathies studied with the dynamic action potential-clamp technique. | |
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MedLine Citation:
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PMID: 18827999 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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The cardiac long QT syndrome (LQTS) is characterized by a delayed repolarization of the ventricular myocytes, resulting in prolongation of the QT interval on the electrocardiogram and increased propensity to cardiac arrhythmias. Congenital LQTS has been linked to mutations in genes encoding ion channel subunits. For a better understanding of LQTS and associated arrhythmias, insight into the nature of ion channel (dys)function is indispensable. Conventionally, voltage-clamp analysis and subsequent mathematical modeling are used to study cardiac channelopathies and to link a certain genetic defect to its cellular phenotype. The recently introduced "dynamic action potential clamp" (dAPC) technique represents an alternative approach, in which a selected native ionic current of the ventricular myocyte can effectively be replaced with wild-type (WT) or mutant current recorded from a human embryonic kidney (HEK)-293 cell that is voltage clamped by the free-running action potential (AP) of the myocyte. Both a computed model of the human ventricular cell and a freshly isolated myocyte can effectively be used in dAPC experiments, resulting in rapid and unambiguous determination of the effect(s) of an ion channel mutation on the ventricular AP. The dAPC technique represents a promising new tool to study various cardiac ion channels and may also prove useful in related fields of research, for example, in neurophysiology. |
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Authors:
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Géza Berecki; Jan G Zegers; Ronald Wilders; Antoni C G Van Ginneken |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: Methods in molecular biology (Clifton, N.J.) Volume: 403 ISSN: 1064-3745 ISO Abbreviation: Methods Mol. Biol. Publication Date: 2007 |
Date Detail:
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Created Date: 2008-10-01 Completed Date: 2008-12-17 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 9214969 Medline TA: Methods Mol Biol Country: United States |
Other Details:
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Languages: eng Pagination: 233-50 Citation Subset: IM |
Affiliation:
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Department of Experimental Cardiology, Academic Medical Center, University of Amsterdam, The Netherlands. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Action Potentials
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physiology* Animals Cell Line Cell Separation Channelopathies / physiopathology* Heart Diseases / physiopathology* Humans Myocytes, Cardiac / physiology Patch-Clamp Techniques / methods* Plasmids / genetics Rabbits Transfection |
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