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Mutations in ion channels involved in the generation and termination of action potentials constitute a family of molecular defects that underlie fatal cardiac arrhythmias in inherited long-QT syndrome. We report here that a loss-of-function (E1425G) mutation in ankyrin-B (also known as ankyrin 2), a member of a family of versatile membrane adapters, causes(More)
BACKGROUND The SCN5A gene encoding the human cardiac sodium channel alpha subunit plays a key role in cardiac electrophysiology. Mutations in SCN5A lead to a large spectrum of phenotypes, including long-QT syndrome, Brugada syndrome, and isolated progressive cardiac conduction defect (Lenègre disease). METHODS AND RESULTS In the present study, we report(More)
Phosphatidylinositol-4,5-bisphosphate (PIP(2)) is a major signaling molecule implicated in the regulation of various ion transporters and channels. Here we show that PIP(2) and intracellular MgATP control the activity of the KCNQ1/KCNE1 potassium channel complex. In excised patch-clamp recordings, the KCNQ1/KCNE1 current decreased spontaneously with time.(More)
The effects of 0.15-250 microM riluzole, a novel psychotropic agent with anticonvulsant properties, were studied on voltage-clamped nodes of Ranvier of isolated nerve fibres of the frog. When added to the external solution, the drug rapidly and reversibly inhibited both K and Na currents with an apparent dissociation constant of 0.09 mM. The(More)
BACKGROUND The SCN5A sodium channel is a major determinant for cardiac impulse propagation. We used epicardial mapping of the atria, ventricles, and septae to investigate conduction velocity (CV) in Scn5a heterozygous young and old mice. METHODS AND RESULTS Mice were divided into 4 groups: (1) young (3 to 4 months) wild-type littermates (WT); (2) young(More)
BACKGROUND The electrocardiographic short QT-interval syndrome forms a distinct clinical entity presenting with a high rate of sudden death and exceptionally short QT intervals. The disorder has recently been linked to gain-of-function mutation in KCNH2. The present study demonstrates that this disorder is genetically heterogeneous and can also be caused by(More)
It has been suggested in a previous article [Escande et al., Am. J. Physiol. 249 (Heart Circ. Physiol. 18): H843-H850, 1985] that transient outward currents may participate in the initial repolarization of human atrial fibers. The present study substantiates the existence of such currents in human myocardium. Membrane currents were recorded in enzymatically(More)
Although electrophysiological remodeling occurs in various myocardial diseases, the underlying molecular mechanisms are poorly understood. cDNA microarrays containing probes for a large population of mouse genes encoding ion channel subunits ("IonChips") were developed and exploited to investigate remodeling of ion channel transcripts associated with(More)
and the other speakers in the sessions and the chairs of the workshops (see Appendix) Preamble 1 The Policy Conference on 'The Potential for QT Prolongation and Proarrhythmia by Non-antiarrhythmic Drugs. The scientific and clinical basis of drug-induced QT prolongation and proarrhythmia was summarized by formal presentations. The speakers were chosen for(More)