Click here to close
Hello! We notice that you are using Internet Explorer, which is not supported by Xenbase and may cause the site to display incorrectly.
We suggest using a current version of Chrome,
FireFox, or Safari.
Fast inactivation causes rectification of the IKr channel.
Spector PS
,
Curran ME
,
Zou A
,
Keating MT
,
Sanguinetti MC
.
???displayArticle.abstract???
The mechanism of rectification of HERG, the human cardiac delayed rectifier K+ channel, was studied after heterologous expression in Xenopus oocytes. Currents were measured using two-microelectrode and macropatch voltage clamp techniques. The fully activated current-voltage (I-V) relationship for HERG inwardly rectified. Rectification was not altered by exposing the cytoplasmic side of a macropatch to a divalent-free solution, indicating this property was not caused by voltage-dependent block of outward current by Mg2+ or other soluble cytosolic molecules. The instantaneous I-V relationship for HERG was linear after removal of fast inactivation by a brief hyperpolarization. The time constants for the onset of and recovery from inactivation were a bell-shaped function of membrane potential. The time constants of inactivation varied from 1.8 ms at +50 mV to 16 ms at -20 mV; recovery from inactivation varied from 4.7 ms at -120 mV to 15 ms at -50 mV. Truncation of the NH2-terminal region of HERG shifted the voltage dependence of activation and inactivation by +20 to +30 mV. In addition, the rate of deactivation of the truncated channel was much faster than wild-type HERG. The mechanism of HERG rectification is voltage-gated fast inactivation. Inactivation of channels proceeds at a much faster rate than activation, such that no outward current is observed upon depolarization to very high membrane potentials. Fast inactivation of HERG and the resulting rectification are partly responsible for the prolonged plateau phase typical of ventricular action potentials.
Anderson,
Functional expression of a probable Arabidopsis thaliana potassium channel in Saccharomyces cerevisiae.
1992, Pubmed
Anderson,
Functional expression of a probable Arabidopsis thaliana potassium channel in Saccharomyces cerevisiae.
1992,
Pubmed
Brüggemann,
Ether-à-go-go encodes a voltage-gated channel permeable to K+ and Ca2+ and modulated by cAMP.
1993,
Pubmed
,
Xenbase
Cao,
Amino terminus and the first four membrane-spanning segments of the Arabidopsis K+ channel KAT1 confer inward-rectification property of plant-animal chimeric channels.
1995,
Pubmed
,
Xenbase
Curran,
A molecular basis for cardiac arrhythmia: HERG mutations cause long QT syndrome.
1995,
Pubmed
Fakler,
Strong voltage-dependent inward rectification of inward rectifier K+ channels is caused by intracellular spermine.
1995,
Pubmed
,
Xenbase
Ficker,
Spermine and spermidine as gating molecules for inward rectifier K+ channels.
1994,
Pubmed
,
Xenbase
FRANKENHAEUSER,
The action of calcium on the electrical properties of squid axons.
1957,
Pubmed
Hoshi,
Regulation of voltage dependence of the KAT1 channel by intracellular factors.
1995,
Pubmed
,
Xenbase
Hoshi,
Biophysical and molecular mechanisms of Shaker potassium channel inactivation.
1990,
Pubmed
,
Xenbase
Lu,
Electrostatic tuning of Mg2+ affinity in an inward-rectifier K+ channel.
1994,
Pubmed
,
Xenbase
Mazzanti,
Intracellular Ca modulates K-inward rectification in cardiac myocytes.
1989,
Pubmed
Sanguinetti,
Two components of cardiac delayed rectifier K+ current. Differential sensitivity to block by class III antiarrhythmic agents.
1990,
Pubmed
Sanguinetti,
A mechanistic link between an inherited and an acquired cardiac arrhythmia: HERG encodes the IKr potassium channel.
1995,
Pubmed
,
Xenbase
Sanguinetti,
Delayed rectifier outward K+ current is composed of two currents in guinea pig atrial cells.
1991,
Pubmed
Schroeder,
Magnesium-independent activation of inward-rectifying K+ channels in Vicia faba guard cells.
1995,
Pubmed
Shibasaki,
Conductance and kinetics of delayed rectifier potassium channels in nodal cells of the rabbit heart.
1987,
Pubmed
Shrier,
Repolarization currents in embryonic chick atrial heart cell aggregates.
1986,
Pubmed
Trudeau,
HERG, a human inward rectifier in the voltage-gated potassium channel family.
1995,
Pubmed
Vandenberg,
Inward rectification of a potassium channel in cardiac ventricular cells depends on internal magnesium ions.
1987,
Pubmed
Wang,
Rapid and slow components of delayed rectifier current in human atrial myocytes.
1994,
Pubmed
Wible,
Gating of inwardly rectifying K+ channels localized to a single negatively charged residue.
1994,
Pubmed
,
Xenbase