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.
K+ channel inactivation mediated by the concerted action of the cytoplasmic N- and C-terminal domains.
Jerng HH
,
Covarrubias M
.
???displayArticle.abstract???
We have examined the molecular mechanism of rapid inactivation gating in a mouse Shal K+ channel (mKv4.1). The results showed that inactivation of these channels follows a complex time course that is well approximated by the sum of three exponential terms. Truncation of an amphipathic region at the N-terminus (residues 2-71) abolished the rapid phase of inactivation (r = 16 ms) and altered voltage-dependent gating. Surprisingly, these effects could be mimicked by deletions affecting the hydrophilic C-terminus. The sum of two exponential terms was sufficient to describe the inactivation of deletion mutants. In fact, the time constants corresponded closely to those of the intermediate and slow phases of inactivation observed with wild-type channels. Further analysis revealed that several basic amino acids at the N-terminus do not influence inactivation, but a positively charged domain at the C-terminus (amino acids 420-550) is necessary to support rapid inactivation. Thus, the amphipathic N-terminus and the hydrophilic C-terminus of mKv4.1 are essential determinants of inactivation gating and may interact with each other to maintain the N-terminal inactivation gate near the inner mouth of the channel. Furthermore, this inactivation gate may not behave like a simple open-channel blocker because channel blockade by internal tetraethylammonium was not associated with slower current decay and an elevated external K+ concentration retarded recovery from inactivation.
Baldwin,
Characterization of a mammalian cDNA for an inactivating voltage-sensitive K+ channel.
1991, Pubmed,
Xenbase
Baldwin,
Characterization of a mammalian cDNA for an inactivating voltage-sensitive K+ channel.
1991,
Pubmed
,
Xenbase
Baro,
Lobster shal: comparison with Drosophila shal and native potassium currents in identified neurons.
1996,
Pubmed
,
Xenbase
Baukrowitz,
Modulation of K+ current by frequency and external [K+]: a tale of two inactivation mechanisms.
1995,
Pubmed
Chabala,
Low molecular weight poly(A)+ mRNA species encode factors that modulate gating of a non-Shaker A-type K+ channel.
1993,
Pubmed
,
Xenbase
Choi,
Tetraethylammonium blockade distinguishes two inactivation mechanisms in voltage-activated K+ channels.
1991,
Pubmed
Covarrubias,
Elimination of rapid potassium channel inactivation by phosphorylation of the inactivation gate.
1994,
Pubmed
,
Xenbase
Demo,
The inactivation gate of the Shaker K+ channel behaves like an open-channel blocker.
1991,
Pubmed
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
Hoshi,
Biophysical and molecular mechanisms of Shaker potassium channel inactivation.
1990,
Pubmed
,
Xenbase
Iverson,
The role of the divergent amino and carboxyl domains on the inactivation properties of potassium channels derived from the Shaker gene of Drosophila.
1990,
Pubmed
,
Xenbase
Kowdley,
Hyperpolarization-activated chloride currents in Xenopus oocytes.
1994,
Pubmed
,
Xenbase
Liu,
Dynamic rearrangement of the outer mouth of a K+ channel during gating.
1996,
Pubmed
López-Barneo,
Effects of external cations and mutations in the pore region on C-type inactivation of Shaker potassium channels.
1993,
Pubmed
,
Xenbase
MacKinnon,
Functional stoichiometry of Shaker potassium channel inactivation.
1993,
Pubmed
,
Xenbase
Murrell-Lagnado,
Energetics of Shaker K channels block by inactivation peptides.
1993,
Pubmed
,
Xenbase
Murrell-Lagnado,
Interactions of amino terminal domains of Shaker K channels with a pore blocking site studied with synthetic peptides.
1993,
Pubmed
,
Xenbase
Ogielska,
Cooperative subunit interactions in C-type inactivation of K channels.
1995,
Pubmed
,
Xenbase
O'Leary,
A molecular link between activation and inactivation of sodium channels.
1995,
Pubmed
Pak,
mShal, a subfamily of A-type K+ channel cloned from mammalian brain.
1991,
Pubmed
Panyi,
C-type inactivation of a voltage-gated K+ channel occurs by a cooperative mechanism.
1995,
Pubmed
Ruppersberg,
Cloned neuronal IK(A) channels reopen during recovery from inactivation.
1991,
Pubmed
Salkoff,
An essential 'set' of K+ channels conserved in flies, mice and humans.
1992,
Pubmed
,
Xenbase
Serôdio,
Identification of molecular components of A-type channels activating at subthreshold potentials.
1994,
Pubmed
,
Xenbase
Serôdio,
Cloning of a novel component of A-type K+ channels operating at subthreshold potentials with unique expression in heart and brain.
1996,
Pubmed
,
Xenbase
Shen,
Deletion analysis of K+ channel assembly.
1993,
Pubmed
,
Xenbase
Sheng,
Subcellular segregation of two A-type K+ channel proteins in rat central neurons.
1992,
Pubmed
,
Xenbase
Spector,
Fast inactivation causes rectification of the IKr channel.
1996,
Pubmed
,
Xenbase
Tseng-Crank,
Functional role of the NH2-terminal cytoplasmic domain of a mammalian A-type K channel.
1993,
Pubmed
,
Xenbase
VanDongen,
Alteration and restoration of K+ channel function by deletions at the N- and C-termini.
1990,
Pubmed
West,
A cluster of hydrophobic amino acid residues required for fast Na(+)-channel inactivation.
1992,
Pubmed
,
Xenbase
Xu,
Assembly of voltage-gated potassium channels. Conserved hydrophilic motifs determine subfamily-specific interactions between the alpha-subunits.
1995,
Pubmed
Zagotta,
Restoration of inactivation in mutants of Shaker potassium channels by a peptide derived from ShB.
1990,
Pubmed
,
Xenbase
