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A mechanistic link between an inherited and an acquird cardiac arrthytmia: HERG encodes the IKr potassium channel
TLDR
The finding that HERG encodes IKr channels provides a mechanistic link between certain forms of inherited and acquired LQT, and that an additional subunit may be required for drug sensitivity. Expand
Two components of cardiac delayed rectifier K+ current. Differential sensitivity to block by class III antiarrhythmic agents
TLDR
The magnitude of IKr was small relative to fully activated IKs, and the two currents were of similar magnitude when measured during a relatively short pulse protocol at membrane potentials typical of the plateau phase of cardiac action potentials. Expand
CaV1.2 Calcium Channel Dysfunction Causes a Multisystem Disorder Including Arrhythmia and Autism
TLDR
Functional expression reveals that G406R produces maintained inward Ca(2+) currents by causing nearly complete loss of voltage-dependent channel inactivation, which likely induces intracellular Ca( 2+) overload in multiple cell types. Expand
A structural basis for drug-induced long QT syndrome.
TLDR
Alanine-scanning mutagenesis is used to determine the structural basis for high-affinity drug block of HERG channels by MK-499, a methanesulfonanilide antiarrhythmic drug, and suggest a possible structural explanation for how so many commonly used medications block HERG but not other Kv channels. Expand
hERG potassium channels and cardiac arrhythmia
TLDR
Insights gained from the crystal structures of other potassium channels have helped understanding of the block of hERG channels and the mechanisms of gating. Expand
Coassembly of KVLQT1 and minK (IsK) proteins to form cardiac IKS potassium channel
TLDR
KVLQT1 is the subunit that coassembles with minK to form IKS channels and IKS dysfunction is a cause of cardiac arrhythmia, and is shown to encode a K+ channel with biophysical properties unlike other known cardiac currents. Expand
Coassembly of K(V)LQT1 and minK (IsK) proteins to form cardiac I(Ks) potassium channel.
TLDR
K(V)LQT1 is the subunit that coassembles with minK to form I(Ks) channels and I( Ks) dysfunction is a cause of cardiac arrhythmia. Expand
Severe arrhythmia disorder caused by cardiac L-type calcium channel mutations.
TLDR
Computer modeling showed prolongation of cardiomyocyte action potentials and delayed afterdepolarizations, factors that increase risk of arrhythmia, and data indicate that gain-of-function mutations of CaV1.2 exons 8 and 8A cause distinct forms of TS. Expand
Loss-of-Function Mutations in the Cardiac Calcium Channel Underlie a New Clinical Entity Characterized by ST-Segment Elevation, Short QT Intervals, and Sudden Cardiac Death
TLDR
This is the first report of loss-of-function mutations in genes encoding the cardiac L-type calcium channel to be associated with a familial sudden cardiac death syndrome in which a Brugada syndrome phenotype is combined with shorter-than-normal QT intervals. Expand
Fast inactivation causes rectification of the IKr channel
TLDR
The mechanism of rectification of HERG, the human cardiac delayed rectifier K+ channel, was studied after heterologous expression in Xenopus oocytes, showing voltage-gated fast inactivation and the resulting rectification are partly responsible for the prolonged plateau phase typical of ventricular action potentials. Expand
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