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.
Functional characterization of the C-terminus of the human ether-à-go-go-related gene K(+) channel (HERG).
Aydar E, Palmer C.
???displayArticle.abstract???
1. In the present study the functional role of the C-terminus of the human ether-à-go-go-related gene K(+) channel HERG was investigated using a series of C-terminal deletion constructs expressed in Xenopus oocytes. 2. Constructs with deletions of 311 or more amino acid residues failed to form functional channels. Truncation by 215 amino acid residues or fewer had no discernable effects on channel activity. Truncation by 236 or 278 amino acid residues accelerated deactivation, and caused a faster recovery from inactivation. 3. In high extracellular K(+), channel deactivation of HERG results from the binding of the N-terminus to a site within the pore. This slows channel deactivation by a knock-off mechanism. Here, it was shown that C-terminal deletions also abolished this effect of high extracellular K(+). Mutants containing deletions in both the N- and C-termini deactivated with rates similar to those observed in individual deletion mutants. 4. In contrast, experiments with double-deletion constructs showed additive effects of the N- and C-termini on the voltage dependence of activation, and on the kinetics of inactivation and recovery from inactivation. The reduction of inactivation in these mutants contributed to an increase in peak current amplitude. 5. These results indicate that residues within the C-terminus of HERG play a role in channel expression as well as in most aspects of channel gating. The regulation of channel deactivation is likely to be mediated by an interaction with the N-terminus, but the regulation of the voltage dependence of activation, and of rate processes associated with inactivation, does not require the N-terminus.
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 Anderson,
Functional expression of a probable Arabidopsis thaliana potassium channel in Saccharomyces cerevisiae.
1992,
Pubmed Armstrong,
Time course of TEA(+)-induced anomalous rectification in squid giant axons.
1966,
Pubmed Arnold,
Molecular determinants for subcellular localization of PSD-95 with an interacting K+ channel.
1999,
Pubmed Bentley,
Determinants of potassium channel assembly localised within the cytoplasmic C-terminal domain of Kv2.1.
1999,
Pubmed
,
Xenbase Berthet,
C-terminal HERG mutations: the role of hypokalemia and a KCNQ1-associated mutation in cardiac event occurrence.
1999,
Pubmed Chen,
Long QT syndrome-associated mutations in the Per-Arnt-Sim (PAS) domain of HERG potassium channels accelerate channel deactivation.
1999,
Pubmed
,
Xenbase Cui,
Cyclic AMP regulates the HERG K(+) channel by dual pathways.
2000,
Pubmed Curran,
A molecular basis for cardiac arrhythmia: HERG mutations cause long QT syndrome.
1995,
Pubmed Daram,
Tetramerization of the AKT1 plant potassium channel involves its C-terminal cytoplasmic domain.
1997,
Pubmed Demo,
The inactivation gate of the Shaker K+ channel behaves like an open-channel blocker.
1991,
Pubmed Gulbis,
Structure of the cytoplasmic beta subunit-T1 assembly of voltage-dependent K+ channels.
2000,
Pubmed
,
Xenbase Hopkins,
Both N- and C-terminal regions contribute to the assembly and functional expression of homo- and heteromultimeric voltage-gated K+ channels.
1994,
Pubmed
,
Xenbase Hoshi,
Two types of inactivation in Shaker K+ channels: effects of alterations in the carboxy-terminal region.
1991,
Pubmed
,
Xenbase Itoh,
Genomic organization and mutational analysis of HERG, a gene responsible for familial long QT syndrome.
1998,
Pubmed Jan,
Voltage-gated and inwardly rectifying potassium channels.
1997,
Pubmed Jerng,
K+ channel inactivation mediated by the concerted action of the cytoplasmic N- and C-terminal domains.
1997,
Pubmed
,
Xenbase Kaupp,
Primary structure and functional expression from complementary DNA of the rod photoreceptor cyclic GMP-gated channel.
1989,
Pubmed
,
Xenbase Kiehn,
HERG potassium channel activation is shifted by phorbol esters via protein kinase A-dependent pathways.
1998,
Pubmed
,
Xenbase Kim,
Clustering of Shaker-type K+ channels by interaction with a family of membrane-associated guanylate kinases.
1995,
Pubmed Kobertz,
Hanging gondola structure of the T1 domain in a voltage-gated K(+) channel.
2000,
Pubmed
,
Xenbase 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 Liman,
Subunit stoichiometry of a mammalian K+ channel determined by construction of multimeric cDNAs.
1992,
Pubmed
,
Xenbase Liu,
Subunit stoichiometry of cyclic nucleotide-gated channels and effects of subunit order on channel function.
1996,
Pubmed Ludwig,
Carboxy-terminal domain mediates assembly of the voltage-gated rat ether-à-go-go potassium channel.
1997,
Pubmed MacKinnon,
Mechanism of charybdotoxin block of the high-conductance, Ca2+-activated K+ channel.
1988,
Pubmed MacKinnon,
New insights into the structure and function of potassium channels.
1991,
Pubmed Marten,
Voltage-dependent gating characteristics of the K+ channel KAT1 depend on the N and C termini.
1997,
Pubmed Miller,
Conversion of a delayed rectifier K+ channel to a voltage-gated inward rectifier K+ channel by three amino acid substitutions.
1996,
Pubmed Minor,
The polar T1 interface is linked to conformational changes that open the voltage-gated potassium channel.
2000,
Pubmed
,
Xenbase Pajor,
Molecular biology approaches to comparative study of Na(+)-glucose cotransport.
1992,
Pubmed Perozo,
Gating currents in Shaker K+ channels. Implications for activation and inactivation models.
1992,
Pubmed
,
Xenbase Ranganathan,
Spatial localization of the K+ channel selectivity filter by mutant cycle-based structure analysis.
1996,
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 Satler,
Novel missense mutation in the cyclic nucleotide-binding domain of HERG causes long QT syndrome.
1996,
Pubmed Schönherr,
Molecular determinants for activation and inactivation of HERG, a human inward rectifier potassium channel.
1996,
Pubmed
,
Xenbase Sentenac,
Cloning and expression in yeast of a plant potassium ion transport system.
1992,
Pubmed Spector,
Fast inactivation causes rectification of the IKr channel.
1996,
Pubmed
,
Xenbase Terlau,
Amino terminal-dependent gating of the potassium channel rat eag is compensated by a mutation in the S4 segment.
1997,
Pubmed
,
Xenbase Thomas,
Deletion of protein kinase A phosphorylation sites in the HERG potassium channel inhibits activation shift by protein kinase A.
1999,
Pubmed
,
Xenbase Trudeau,
HERG, a human inward rectifier in the voltage-gated potassium channel family.
1995,
Pubmed VanDongen,
Alteration and restoration of K+ channel function by deletions at the N- and C-termini.
1990,
Pubmed Wang,
Regulation of deactivation by an amino terminal domain in human ether-à-go-go-related gene potassium channels.
1998,
Pubmed
,
Xenbase Warmke,
A family of potassium channel genes related to eag in Drosophila and mammals.
1994,
Pubmed Wood,
Mutations and deletions within the S8-S9 interdomain region abolish complementation of N- and C-terminal domains of Ca(2+)-activated K+ (BK) channels.
1997,
Pubmed
,
Xenbase Zhou,
HERG channel dysfunction in human long QT syndrome. Intracellular transport and functional defects.
1998,
Pubmed
