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.
Participation of HERG channel cytoplasmic structures on regulation by the G protein-coupled TRH receptor.
Alonso-Ron C
,
Barros F
,
Manso DG
,
Gómez-Varela D
,
Miranda P
,
Carretero L
,
Domínguez P
,
de la Peña P
.
???displayArticle.abstract???
Human ether-a-go-go-related gene (HERG) channels heterologously expressed in Xenopus oocytes are regulated by the activation of G protein-coupled hormone receptors that, like the thyrotropin-releasing hormone (TRH) receptor, activate phospholipase C. Previous work with serially deleted HERG mutants suggested that residues 326-345 located in the proximal domain of the channels amino terminus might be required for the hormonal modulation of HERG activation. Generation of new channel mutants deleted in this region further point to the amino acid sequence between residues 326 and 332 as a possible determinant of the TRH effects, but individual or combined single-point mutations in this sequence demonstrate that maintenance of its consensus sites for phosphorylation and/or interaction with regulatory components is not important for the modulatory response(s). The TRH-induced effects also remained unaltered when a basic amino acid cluster located between residues 362 and 366 is eliminated. Additionally, no effect of TRH was observed in channels carrying single-point mutations at the beginning of the intracellular loop linking transmembrane domains S4 and S5. Our results indicate that a correct structural arrangement of the amino terminal domains is essential for the hormone-induced modifications of HERG activation. They also suggest that the hormonal regulatory action is transmitted to the transmembrane channel core through interactions between the cytoplasmic domains and the initial portion of the S4-S5 linker.
Alonso-Ron,
Thermodynamic and kinetic properties of amino-terminal and S4-S5 loop HERG channel mutants under steady-state conditions.
2008, Pubmed,
Xenbase
Alonso-Ron,
Thermodynamic and kinetic properties of amino-terminal and S4-S5 loop HERG channel mutants under steady-state conditions.
2008,
Pubmed
,
Xenbase
Barros,
Demonstration of an inwardly rectifying K+ current component modulated by thyrotropin-releasing hormone and caffeine in GH3 rat anterior pituitary cells.
1997,
Pubmed
Barros,
Modulation of human erg K+ channel gating by activation of a G protein-coupled receptor and protein kinase C.
1998,
Pubmed
,
Xenbase
Barros,
The role of the inwardly rectifying K+ current in resting potential and thyrotropin-releasing-hormone-induced changes in cell excitability of GH3 rat anterior pituitary cells.
1994,
Pubmed
Bauer,
A functional role of the erg-like inward-rectifying K+ current in prolactin secretion from rat lactotrophs.
1999,
Pubmed
Bian,
HERG K(+) channel activity is regulated by changes in phosphatidyl inositol 4,5-bisphosphate.
2001,
Pubmed
Cayabyab,
Regulation of an ERG K+ current by Src tyrosine kinase.
2002,
Pubmed
Cherubini,
HERG potassium channels are more frequently expressed in human endometrial cancer as compared to non-cancerous endometrium.
2000,
Pubmed
Chiang,
The long QT syndromes: genetic basis and clinical implications.
2000,
Pubmed
de la Peña,
Cloning and expression of the thyrotropin-releasing hormone receptor from GH3 rat anterior pituitary cells.
1992,
Pubmed
,
Xenbase
de la Peña,
Two isoforms of the thyrotropin-releasing hormone receptor generated by alternative splicing have indistinguishable functional properties.
1992,
Pubmed
,
Xenbase
de la Peña,
Gs couples thyrotropin-releasing hormone receptors expressed in Xenopus oocytes to phospholipase C.
1995,
Pubmed
,
Xenbase
Emmi,
Do glia have heart? Expression and functional role for ether-a-go-go currents in hippocampal astrocytes.
2000,
Pubmed
Finlayson,
Acquired QT interval prolongation and HERG: implications for drug discovery and development.
2004,
Pubmed
Gomez-Varela,
Protein kinase C is necessary for recovery from the thyrotropin-releasing hormone-induced r-ERG current reduction in GH3 rat anterior pituitary cells.
2003,
Pubmed
Gómez-Varela,
Relevance of the proximal domain in the amino-terminus of HERG channels for regulation by a phospholipase C-coupled hormone receptor.
2003,
Pubmed
,
Xenbase
Gómez-Varela,
Influence of amino-terminal structures on kinetic transitions between several closed and open states in human erg K+ channels.
2002,
Pubmed
,
Xenbase
Jiang,
Use-dependent 'agonist' effect of azimilide on the HERG channel.
1999,
Pubmed
,
Xenbase
Kagan,
14-3-3 amplifies and prolongs adrenergic stimulation of HERG K+ channel activity.
2002,
Pubmed
Keating,
Molecular and cellular mechanisms of cardiac arrhythmias.
2001,
Pubmed
Kemp,
Protein kinase recognition sequence motifs.
1990,
Pubmed
Kennelly,
Consensus sequences as substrate specificity determinants for protein kinases and protein phosphatases.
1991,
Pubmed
Kiehn,
Regulation of the cardiac repolarizing HERG potassium channel by protein kinase A.
2000,
Pubmed
Long,
Voltage sensor of Kv1.2: structural basis of electromechanical coupling.
2005,
Pubmed
Miranda,
Specificity of TRH receptor coupling to G-proteins for regulation of ERG K+ channels in GH3 rat anterior pituitary cells.
2005,
Pubmed
Morais Cabral,
Crystal structure and functional analysis of the HERG potassium channel N terminus: a eukaryotic PAS domain.
1998,
Pubmed
,
Xenbase
Morita,
The QT syndromes: long and short.
2008,
Pubmed
Overholt,
HERG-Like potassium current regulates the resting membrane potential in glomus cells of the rabbit carotid body.
2000,
Pubmed
Redfern,
Relationships between preclinical cardiac electrophysiology, clinical QT interval prolongation and torsade de pointes for a broad range of drugs: evidence for a provisional safety margin in drug development.
2003,
Pubmed
Roden,
Multiple mechanisms in the long-QT syndrome. Current knowledge, gaps, and future directions. The SADS Foundation Task Force on LQTS.
1996,
Pubmed
Rosati,
Glucose- and arginine-induced insulin secretion by human pancreatic beta-cells: the role of HERG K(+) channels in firing and release.
2000,
Pubmed
Saenen,
Modulation of HERG gating by a charge cluster in the N-terminal proximal domain.
2006,
Pubmed
Sanguinetti,
Mutations of the S4-S5 linker alter activation properties of HERG potassium channels expressed in Xenopus oocytes.
1999,
Pubmed
,
Xenbase
Sanguinetti,
A mechanistic link between an inherited and an acquired cardiac arrhythmia: HERG encodes the IKr potassium channel.
1995,
Pubmed
,
Xenbase
Schäfer,
The erg-like potassium current in rat lactotrophs.
1999,
Pubmed
Schledermann,
Modulation of rat erg1, erg2, erg3 and HERG K+ currents by thyrotropin-releasing hormone in anterior pituitary cells via the native signal cascade.
2001,
Pubmed
Schwartz,
Management of long QT syndrome.
2005,
Pubmed
Thomas,
Adrenergic regulation of the rapid component of the cardiac delayed rectifier potassium current, I(Kr), and the underlying hERG ion channel.
2004,
Pubmed
Thomas,
Regulation of HERG potassium channel activation by protein kinase C independent of direct phosphorylation of the channel protein.
2003,
Pubmed
,
Xenbase
Tristani-Firouzi,
Interactions between S4-S5 linker and S6 transmembrane domain modulate gating of HERG K+ channels.
2002,
Pubmed
,
Xenbase
Trudeau,
HERG, a human inward rectifier in the voltage-gated potassium channel family.
1995,
Pubmed
Viloria,
Differential effects of amino-terminal distal and proximal domains in the regulation of human erg K(+) channel gating.
2000,
Pubmed
,
Xenbase
Viskin,
Long QT syndromes and torsade de pointes.
1999,
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
Zhang,
Normal function of HERG K+ channels expressed in HEK293 cells requires basal protein kinase B activity.
2003,
Pubmed
