Cardiac channelopathies studied with the dynamic action potential-clamp technique

Berecki, G, Zegers, J, Wilders, R and van Ginneken, A 2007, 'Cardiac channelopathies studied with the dynamic action potential-clamp technique', Methods in Molecular Biology, vol. 403, pp. 233-250.


Document type: Journal Article
Collection: Journal Articles

Title Cardiac channelopathies studied with the dynamic action potential-clamp technique
Author(s) Berecki, G
Zegers, J
Wilders, R
van Ginneken, A
Year 2007
Journal name Methods in Molecular Biology
Volume number 403
Start page 233
End page 250
Total pages 18
Publisher Humana Press
Abstract 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.
Subject Biochemistry and Cell Biology not elsewhere classified
Biological Sciences not elsewhere classified
Keyword(s) action potential
animal
article
cell line
cell separation
channelopathy
genetic transfection
genetics
heart disease
heart muscle cell
human
methodology
patch clamp
pathophysiology
physiology
plasmid
rabbit
Copyright notice © 2007 Humana Press
ISSN 1064-3745
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