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Biophys J
1998 Aug 01;752:785-92. doi: 10.1016/S0006-3495(98)77568-X.
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Activation and inactivation of homomeric KvLQT1 potassium channels.
Pusch M
,
Magrassi R
,
Wollnik B
,
Conti F
.
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The voltage-gated potassium channel protein KvLQT1 (Wang et al., 1996. Nature Genet. 12:17-23) is believed to underlie the delayed rectifier potassium current of cardiac muscle together with the small membrane protein minK (also named IsK) as an essential auxiliary subunit (Barhanin et al., 1996. Nature. 384:78-80; Sanguinetti et al., 1996. Nature. 384:80-83) Using the Xenopus oocyte expression system, we analyzed in detail the gating characteristics of homomeric KvLQT1 channels and of heteromeric KvLQT1/minK channels using two-electrode voltage-clamp recordings. Activation of homomeric KvLQT1 at positive voltages is accompanied by an inactivation process that is revealed by a transient increase in conductance after membrane repolarization to negative values. We studied the recovery from inactivation and the deactivation of the channels during tail repolarizations at -120 mV after conditioning pulses of variable amplitude and duration. Most measurements were made in high extracellular potassium to increase the size of inward tail currents. However, experiments in normal low-potassium solutions showed that, in contrast to classical C-type inactivation, the inactivation of KvLQT1 is independent of extracellular potassium. At +40 mV inactivation develops with a delay of 100 ms. At the same potential, the activation estimated from the amplitude of the late exponential decay of the tail currents follows a less sigmoidal time course, with a late time constant of 300 ms. Inactivation of KvLQT1 is not complete, even at the most positive voltages. The delayed, voltage-dependent onset and the incompleteness of inactivation suggest a sequential gating scheme containing at least two open states and ending with an inactivating step that is voltage independent. In coexpression experiments of KvLQT1 with minK, inactivation seems to be largely absent, although biphasic tails are also observed that could be related to similar phenomena.
Balser,
Time-dependent outward current in guinea pig ventricular myocytes. Gating kinetics of the delayed rectifier.
1990, Pubmed
Balser,
Time-dependent outward current in guinea pig ventricular myocytes. Gating kinetics of the delayed rectifier.
1990,
Pubmed
Barhanin,
K(V)LQT1 and lsK (minK) proteins associate to form the I(Ks) cardiac potassium current.
1996,
Pubmed
,
Xenbase
Baukrowitz,
Modulation of K+ current by frequency and external [K+]: a tale of two inactivation mechanisms.
1995,
Pubmed
Campbell,
Ionic current mechanisms generating vertebrate primary cardiac pacemaker activity at the single cell level: an integrative view.
1992,
Pubmed
Chouabe,
Properties of KvLQT1 K+ channel mutations in Romano-Ward and Jervell and Lange-Nielsen inherited cardiac arrhythmias.
1997,
Pubmed
Curran,
A molecular basis for cardiac arrhythmia: HERG mutations cause long QT syndrome.
1995,
Pubmed
DiFrancesco,
The cardiac hyperpolarizing-activated current, if. Origins and developments.
1985,
Pubmed
Goldstein,
Site-specific mutations in a minimal voltage-dependent K+ channel alter ion selectivity and open-channel block.
1991,
Pubmed
,
Xenbase
Hoshi,
Biophysical and molecular mechanisms of Shaker potassium channel inactivation.
1990,
Pubmed
,
Xenbase
Jurkiewicz,
Rate-dependent prolongation of cardiac action potentials by a methanesulfonanilide class III antiarrhythmic agent. Specific block of rapidly activating delayed rectifier K+ current by dofetilide.
1993,
Pubmed
Kaczmarek,
Properties and regulation of the minK potassium channel protein.
1997,
Pubmed
,
Xenbase
López-Barneo,
Effects of external cations and mutations in the pore region on C-type inactivation of Shaker potassium channels.
1993,
Pubmed
,
Xenbase
McDonald,
A minK-HERG complex regulates the cardiac potassium current I(Kr).
1997,
Pubmed
,
Xenbase
Neyroud,
A novel mutation in the potassium channel gene KVLQT1 causes the Jervell and Lange-Nielsen cardioauditory syndrome.
1997,
Pubmed
Noble,
The surprising heart: a review of recent progress in cardiac electrophysiology.
1984,
Pubmed
Roden,
The cardiac ion channels: relevance to management of arrhythmias.
1996,
Pubmed
Romey,
Molecular mechanism and functional significance of the MinK control of the KvLQT1 channel activity.
1997,
Pubmed
Russell,
KVLQT1 mutations in three families with familial or sporadic long QT syndrome.
1996,
Pubmed
Sanguinetti,
A mechanistic link between an inherited and an acquired cardiac arrhythmia: HERG encodes the IKr potassium channel.
1995,
Pubmed
,
Xenbase
Sanguinetti,
Coassembly of K(V)LQT1 and minK (IsK) proteins to form cardiac I(Ks) potassium channel.
1996,
Pubmed
,
Xenbase
Schulze-Bahr,
KCNE1 mutations cause jervell and Lange-Nielsen syndrome.
1997,
Pubmed
Schönherr,
Molecular determinants for activation and inactivation of HERG, a human inward rectifier potassium channel.
1996,
Pubmed
,
Xenbase
Smith,
The inward rectification mechanism of the HERG cardiac potassium channel.
1996,
Pubmed
Spector,
Fast inactivation causes rectification of the IKr channel.
1996,
Pubmed
,
Xenbase
Splawski,
Mutations in the hminK gene cause long QT syndrome and suppress IKs function.
1997,
Pubmed
,
Xenbase
Tai,
The conduction pore of a cardiac potassium channel.
1998,
Pubmed
,
Xenbase
Takumi,
Cloning of a membrane protein that induces a slow voltage-gated potassium current.
1988,
Pubmed
,
Xenbase
Tanaka,
Four novel KVLQT1 and four novel HERG mutations in familial long-QT syndrome.
1997,
Pubmed
Trudeau,
HERG, a human inward rectifier in the voltage-gated potassium channel family.
1995,
Pubmed
Wang,
Positional cloning of a novel potassium channel gene: KVLQT1 mutations cause cardiac arrhythmias.
1996,
Pubmed
Wang,
Time, voltage and ionic concentration dependence of rectification of h-erg expressed in Xenopus oocytes.
1996,
Pubmed
,
Xenbase
Wang,
A quantitative analysis of the activation and inactivation kinetics of HERG expressed in Xenopus oocytes.
1997,
Pubmed
,
Xenbase
Wollnik,
Pathophysiological mechanisms of dominant and recessive KVLQT1 K+ channel mutations found in inherited cardiac arrhythmias.
1997,
Pubmed
Yang,
KvLQT1, a voltage-gated potassium channel responsible for human cardiac arrhythmias.
1997,
Pubmed
,
Xenbase
van den Berg,
The long QT syndrome: a novel missense mutation in the S6 region of the KVLQT1 gene.
1997,
Pubmed
