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.
Inactivation and recovery in Kv1.4 K+ channels: lipophilic interactions at the intracellular mouth of the pore.
Bett GC
,
Rasmusson RL
.
???displayArticle.abstract???
C-type inactivation is present in many voltage-gated potassium channels and is probably related to 'slow' inactivation in calcium and sodium channels. The mechanisms underlying C-type inactivation are unclear, but it is sensitive to mutations on both the extra- and intracellular sides of the channel. We used an N-terminal deleted channel with a valine to alanine point mutation at the intracellular side of S6 (fKv1.4[V561A]DeltaN). This construct alters recovery from inactivation and inverts the relationship between C-type inactivation and [K(+)](o). We used this inverted relationship to examine C-type inactivation and coupling mechanisms between N- and C-type inactivation. The valine to alanine mutation reduces the channel's affinity for both quinidine and the N-terminal domain. However, binding of the N-terminal or quinidine restores normal recovery from inactivation. This suggests that coupling between N- and C-type inactivation is dominated by allosteric mechanisms. The permeation mechanism, driven by a reduction in permeant [K(+)](o) following pore block (which would retard C-type inactivation), contributes minimally to coupling in these channels. We propose that the cytoplasmic half of S6 forms part of the N-terminal binding site, as previously predicted from X-ray crystallography studies in the distantly related KcsA channel. Binding of the N-terminal domain or a positively charged lipophilic compound such as quinidine interacts with the hydrophobic moieties on S6 in the bound state. This binding can orientate S6 into a conformation which resembles the normal C-type inactivated state. This is the probable mechanism by which drug or N-terminal binding increases the rate of C-type inactivation via an allosteric mechanism.
Adelman,
Episodic ataxia results from voltage-dependent potassium channels with altered functions.
1995, Pubmed,
Xenbase
Adelman,
Episodic ataxia results from voltage-dependent potassium channels with altered functions.
1995,
Pubmed
,
Xenbase
Aldrich,
Differences in gating among amino-terminal variants of Shaker potassium channels.
1990,
Pubmed
,
Xenbase
Armstrong,
Time course of TEA(+)-induced anomalous rectification in squid giant axons.
1966,
Pubmed
Armstrong,
Induced inactivation of the potassium permeability of squid axon membranes.
1968,
Pubmed
Armstrong,
Inactivation of the potassium conductance and related phenomena caused by quaternary ammonium ion injection in squid axons.
1969,
Pubmed
Armstrong,
Interaction of tetraethylammonium ion derivatives with the potassium channels of giant axons.
1971,
Pubmed
Barry,
Myocardial potassium channels: electrophysiological and molecular diversity.
1996,
Pubmed
Baukrowitz,
Modulation of K+ current by frequency and external [K+]: a tale of two inactivation mechanisms.
1995,
Pubmed
Baukrowitz,
Two functionally distinct subsites for the binding of internal blockers to the pore of voltage-activated K+ channels.
1996,
Pubmed
Bett,
Functionally-distinct proton-binding in HERG suggests the presence of two binding sites.
2003,
Pubmed
,
Xenbase
Busch,
Current inactivation involves a histidine residue in the pore of the rat lymphocyte potassium channel RGK5.
1991,
Pubmed
,
Xenbase
Caballero,
Putative binding sites for benzocaine on a human cardiac cloned channel (Kv1.5).
2002,
Pubmed
Castle,
4-Aminopyridine binding and slow inactivation are mutually exclusive in rat Kv1.1 and Shaker potassium channels.
1994,
Pubmed
,
Xenbase
Chen,
Position of aromatic residues in the S6 domain, not inactivation, dictates cisapride sensitivity of HERG and eag potassium channels.
2002,
Pubmed
,
Xenbase
Choi,
Tetraethylammonium blockade distinguishes two inactivation mechanisms in voltage-activated K+ channels.
1991,
Pubmed
Claydon,
Inhibition of the K+ channel kv1.4 by acidosis: protonation of an extracellular histidine slows the recovery from N-type inactivation.
2000,
Pubmed
,
Xenbase
Comer,
Cloning and characterization of an Ito-like potassium channel from ferret ventricle.
1994,
Pubmed
,
Xenbase
Demo,
The inactivation gate of the Shaker K+ channel behaves like an open-channel blocker.
1991,
Pubmed
Ficker,
Molecular determinants of dofetilide block of HERG K+ channels.
1998,
Pubmed
,
Xenbase
Ficker,
Molecular determinants of inactivation and dofetilide block in ether a-go-go (EAG) channels and EAG-related K(+) channels.
2001,
Pubmed
,
Xenbase
Gidh-Jain,
Differential expression of voltage-gated K+ channel genes in left ventricular remodeled myocardium after experimental myocardial infarction.
1996,
Pubmed
Heginbotham,
The aromatic binding site for tetraethylammonium ion on potassium channels.
1992,
Pubmed
Holmgren,
N-type inactivation and the S4-S5 region of the Shaker K+ channel.
1996,
Pubmed
Hoshi,
Biophysical and molecular mechanisms of Shaker potassium channel inactivation.
1990,
Pubmed
,
Xenbase
Hoshi,
Two types of inactivation in Shaker K+ channels: effects of alterations in the carboxy-terminal region.
1991,
Pubmed
,
Xenbase
Isacoff,
Putative receptor for the cytoplasmic inactivation gate in the Shaker K+ channel.
1991,
Pubmed
,
Xenbase
Jerng,
K+ channel inactivation mediated by the concerted action of the cytoplasmic N- and C-terminal domains.
1997,
Pubmed
,
Xenbase
Jiang,
C-type inactivation involves a significant decrease in the intracellular aqueous pore volume of Kv1.4 K+ channels expressed in Xenopus oocytes.
2003,
Pubmed
,
Xenbase
Kaprielian,
Relationship between K+ channel down-regulation and [Ca2+]i in rat ventricular myocytes following myocardial infarction.
1999,
Pubmed
Kiehn,
Molecular physiology and pharmacology of HERG. Single-channel currents and block by dofetilide.
1996,
Pubmed
,
Xenbase
Lee,
Downregulation of voltage-gated K(+) channels in rat heart with right ventricular hypertrophy.
1999,
Pubmed
Li,
Regulation of N- and C-type inactivation of Kv1.4 by pHo and K+: evidence for transmembrane communication.
2003,
Pubmed
,
Xenbase
Lipkind,
A structural motif for the voltage-gated potassium channel pore.
1995,
Pubmed
Liu,
Dynamic rearrangement of the outer mouth of a K+ channel during gating.
1996,
Pubmed
Lopez,
Evidence that the S6 segment of the Shaker voltage-gated K+ channel comprises part of the pore.
1994,
Pubmed
,
Xenbase
López-Barneo,
Effects of external cations and mutations in the pore region on C-type inactivation of Shaker potassium channels.
1993,
Pubmed
,
Xenbase
Mitcheson,
A structural basis for drug-induced long QT syndrome.
2000,
Pubmed
,
Xenbase
Morales,
The N-terminal domain of a K+ channel beta subunit increases the rate of C-type inactivation from the cytoplasmic side of the channel.
1996,
Pubmed
,
Xenbase
Nishiyama,
Altered K(+) channel gene expression in diabetic rat ventricle: isoform switching between Kv4.2 and Kv1.4.
2001,
Pubmed
Rasmusson,
Inactivation of voltage-gated cardiac K+ channels.
1998,
Pubmed
Rasmusson,
C-type inactivation controls recovery in a fast inactivating cardiac K+ channel (Kv1.4) expressed in Xenopus oocytes.
1995,
Pubmed
,
Xenbase
Sanguinetti,
A mechanistic link between an inherited and an acquired cardiac arrhythmia: HERG encodes the IKr potassium channel.
1995,
Pubmed
,
Xenbase
Snyders,
High affinity open channel block by dofetilide of HERG expressed in a human cell line.
1996,
Pubmed
,
Xenbase
Sánchez-Chapula,
Molecular determinants of voltage-dependent human ether-a-go-go related gene (HERG) K+ channel block.
2002,
Pubmed
,
Xenbase
Wang,
Modulation of HERG affinity for E-4031 by [K+]o and C-type inactivation.
1997,
Pubmed
,
Xenbase
Wang,
Kv1.4 channel block by quinidine: evidence for a drug-induced allosteric effect.
2003,
Pubmed
,
Xenbase
Wang,
A quantitative analysis of the activation and inactivation kinetics of HERG expressed in Xenopus oocytes.
1997,
Pubmed
,
Xenbase
Yeola,
Molecular analysis of a binding site for quinidine in a human cardiac delayed rectifier K+ channel. Role of S6 in antiarrhythmic drug binding.
1996,
Pubmed
Zagotta,
Restoration of inactivation in mutants of Shaker potassium channels by a peptide derived from ShB.
1990,
Pubmed
,
Xenbase
Zhou,
Potassium channel receptor site for the inactivation gate and quaternary amine inhibitors.
2001,
Pubmed
,
Xenbase
