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Characterization of hERG1a and hERG1b potassium channels-a possible role for hERG1b in the I (Kr) current.
Larsen AP
,
Olesen SP
,
Grunnet M
,
Jespersen T
.
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I (Kr) is the fast component of the delayed rectifier potassium currents responsible for the repolarization of the cardiac muscle. The molecular correlate underlying the I (Kr) current has been identified as the hERG1 channel. Recently, two splice variants of the hERG1 alpha-subunit, hERG1a and hERG1b, have been shown to be co-expressed in human cardiomyocytes. In this paper, we present the electrophysiological characterization of hERG1a, hERG1b, and co-expressed hERG1a/b channels in a mammalian expression system using the whole-cell patch clamp technique. We also quantified the messenger RNA (mRNA) levels of hERG1a and hERG1b in human cardiac tissue, and based on the expressed ratios, we evaluated the resulting currents in Xenopus laevis oocytes. Compared to hERG1a channels, activation was faster for both hERG1b and hERG1a/b channels. The deactivation kinetics was greatly accelerated in the presence of hERG1b, whereas no difference in the time constant of inactivation was observed. The voltage-dependent recovery from inactivation was also similar. However, the time constant of recovery from inactivation was significantly faster for hERG1b channels compared to hERG1a and hERG1a/b. Quantification of hERG1a and hERG1b mRNA in the human heart showed that hERG1b mRNA constitutes, on average, 19% in the right atrium and 12% in the leftventricle of the total hERG1 mRNA. Expression of the observed ratios of hERG1a to hERG1b in X. laevis oocytes showed that these ratios are indeed sufficient to change the deactivation phenotype markedly. The present work suggests that hERG1b is likely to play a role in the formation of the native I (Kr) current.
Abbott,
MiRP1 forms IKr potassium channels with HERG and is associated with cardiac arrhythmia.
1999, Pubmed,
Xenbase
Abbott,
MiRP1 forms IKr potassium channels with HERG and is associated with cardiac arrhythmia.
1999,
Pubmed
,
Xenbase
Aydar,
Functional characterization of the C-terminus of the human ether-à-go-go-related gene K(+) channel (HERG).
2001,
Pubmed
,
Xenbase
Ficker,
Molecular determinants of dofetilide block of HERG K+ channels.
1998,
Pubmed
,
Xenbase
Grunnet,
Apamin interacts with all subtypes of cloned small-conductance Ca2+-activated K+ channels.
2001,
Pubmed
,
Xenbase
Hirdes,
Fast erg K+ currents in rat embryonic serotonergic neurones.
2005,
Pubmed
Jespersen,
Dual-function vector for protein expression in both mammalian cells and Xenopus laevis oocytes.
2002,
Pubmed
,
Xenbase
Jones,
Cardiac IKr channels minimally comprise hERG 1a and 1b subunits.
2004,
Pubmed
Kirchberger,
Effects of TRH on heteromeric rat erg1a/1b K+ channels are dominated by the rerg1b subunit.
2006,
Pubmed
Kupershmidt,
A K+ channel splice variant common in human heart lacks a C-terminal domain required for expression of rapidly activating delayed rectifier current.
1998,
Pubmed
Lees-Miller,
Electrophysiological characterization of an alternatively processed ERG K+ channel in mouse and human hearts.
1997,
Pubmed
,
Xenbase
Li,
Evidence for two components of delayed rectifier K+ current in human ventricular myocytes.
1996,
Pubmed
Liu,
Characteristics of the delayed rectifier current (IKr and IKs) in canine ventricular epicardial, midmyocardial, and endocardial myocytes. A weaker IKs contributes to the longer action potential of the M cell.
1995,
Pubmed
London,
Two isoforms of the mouse ether-a-go-go-related gene coassemble to form channels with properties similar to the rapidly activating component of the cardiac delayed rectifier K+ current.
1997,
Pubmed
,
Xenbase
McDonald,
A minK-HERG complex regulates the cardiac potassium current I(Kr).
1997,
Pubmed
,
Xenbase
Morais Cabral,
Crystal structure and functional analysis of the HERG potassium channel N terminus: a eukaryotic PAS domain.
1998,
Pubmed
,
Xenbase
Pfaffl,
A new mathematical model for relative quantification in real-time RT-PCR.
2001,
Pubmed
Phartiyal,
Heteromeric assembly of human ether-à-go-go-related gene (hERG) 1a/1b channels occurs cotranslationally via N-terminal interactions.
2007,
Pubmed
Pond,
Expression of distinct ERG proteins in rat, mouse, and human heart. Relation to functional I(Kr) channels.
2000,
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
Schönherr,
Molecular determinants for activation and inactivation of HERG, a human inward rectifier potassium channel.
1996,
Pubmed
,
Xenbase
Schönherr,
Functional role of the slow activation property of ERG K+ channels.
1999,
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
Szabó,
Asymmetrical distribution of ion channels in canine and human left-ventricular wall: epicardium versus midmyocardium.
2005,
Pubmed
Trudeau,
HERG, a human inward rectifier in the voltage-gated potassium channel family.
1995,
Pubmed
Wang,
Rapid and slow components of delayed rectifier current in human atrial myocytes.
1994,
Pubmed
Wang,
A quantitative analysis of the activation and inactivation kinetics of HERG expressed in Xenopus oocytes.
1997,
Pubmed
,
Xenbase
Wang,
Regulation of deactivation by an amino terminal domain in human ether-à-go-go-related gene potassium channels.
1998,
Pubmed
,
Xenbase
Weerapura,
A comparison of currents carried by HERG, with and without coexpression of MiRP1, and the native rapid delayed rectifier current. Is MiRP1 the missing link?
2002,
Pubmed
,
Xenbase
Yang,
K+ currents and K+ channel mRNA in cultured atrial cardiac myocytes (AT-1 cells).
1994,
Pubmed
Zou,
A mutation in the pore region of HERG K+ channels expressed in Xenopus oocytes reduces rectification by shifting the voltage dependence of inactivation.
1998,
Pubmed
,
Xenbase
