Key result
The dynamic action potential clamp (dAPC) technique represents a promising alternative to conventional voltage-clamp analysis for studying cardiac ion channels and mutations in ventricular myocytes.
The dynamic action potential clamp technique represents a promising tool for studying cardiac ion channels and linking genetic defects to cellular phenotypes in channelopathies like long QT syndrome.
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Dynamic AP clamp clarifies mutation effects on repolarization; leaves open clinical translation for LQTS management.
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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Berecki et al. (2006) conducted a review in Cardiac channelopathies (Long QT syndrome). Dynamic action potential clamp (dAPC) technique vs. Conventional voltage-clamp analysis and mathematical modeling was evaluated. The dynamic action potential clamp (dAPC) technique represents a promising alternative to conventional voltage-clamp analysis for studying cardiac ion channels and mutations in ventricular myocytes.
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