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.
Biophys J
2011 Jan 05;1001:11-21. doi: 10.1016/j.bpj.2010.11.011.
Show Gene links
Show Anatomy links
A model of the interaction between N-type and C-type inactivation in Kv1.4 channels.
Bett GC
,
Dinga-Madou I
,
Zhou Q
,
Bondarenko VE
,
Rasmusson RL
.
???displayArticle.abstract??? Kv1.4 channels are Shaker-related voltage-gated potassium channels with two distinct inactivation mechanisms. Fast N-type inactivation operates by a ball-and-chain mechanism. Slower C-type inactivation is not so well defined, but involves intracellular and extracellular conformational changes of the channel. We studied the interaction between inactivation mechanisms using two-electrode voltage-clamp of Kv1.4 and Kv1.4ΔN (amino acids 2-146 deleted to remove N-type inactivation) heterologously expressed in Xenopus oocytes. We manipulated C-type inactivation by introducing a lysine-tyrosine point mutation (K532Y, equivalent to Shaker T449Y) that diminishes C-type inactivation. We used experimental data to develop a comprehensive computer model of Kv1.4 channels to determine the interaction between activation and N- and C-type inactivation mechanisms needed to replicate the experimental data. C-type inactivation began at lower voltage preactivated states, whereas N-type inactivation was coupled directly to the open state. A model with distinct N- and C-type inactivated states was not able to reproduce experimental data, and direct transitions between N- and C-type inactivated states were required, i.e., there is coupling between N- and C-type inactivated states. C-type inactivation is the rate-limiting step determining recovery from inactivation, so understanding C-type inactivation, and how it is coupled to N-type inactivation, is critical in understanding how channels act to repetitive stimulation.
Ayer,
Enhanced closed-state inactivation in a mutant Shaker K+ channel.
1997, Pubmed,
Xenbase
Ayer,
Enhanced closed-state inactivation in a mutant Shaker K+ channel.
1997,
Pubmed
,
Xenbase
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
Bett,
Modification of K+ channel-drug interactions by ancillary subunits.
2008,
Pubmed
Bett,
Functionally-distinct proton-binding in HERG suggests the presence of two binding sites.
2003,
Pubmed
,
Xenbase
Bett,
Inactivation and recovery in Kv1.4 K+ channels: lipophilic interactions at the intracellular mouth of the pore.
2004,
Pubmed
,
Xenbase
Bezanilla,
Voltage-gated ion channels.
2005,
Pubmed
Busch,
Current inactivation involves a histidine residue in the pore of the rat lymphocyte potassium channel RGK5.
1991,
Pubmed
,
Xenbase
Castellino,
Time- and voltage-dependent modulation of a Kv1.4 channel by a beta-subunit (Kv beta 3) cloned from ferret ventricle.
1995,
Pubmed
,
Xenbase
Chapman,
Activation-dependent subconductance levels in the drk1 K channel suggest a subunit basis for ion permeation and gating.
1997,
Pubmed
,
Xenbase
Choi,
Tetraethylammonium blockade distinguishes two inactivation mechanisms in voltage-activated K+ channels.
1991,
Pubmed
Comer,
Cloning and characterization of an Ito-like potassium channel from ferret ventricle.
1994,
Pubmed
,
Xenbase
Crouzy,
Fluctuations in ion channel gating currents. Analysis of nonstationary shot noise.
1993,
Pubmed
D'Adamo,
Episodic ataxia type-1 mutations in the hKv1.1 cytoplasmic pore region alter the gating properties of the channel.
1998,
Pubmed
,
Xenbase
Dixon,
Quantitative analysis of potassium channel mRNA expression in atrial and ventricular muscle of rats.
1994,
Pubmed
Dougherty,
Gating charge immobilization in Kv4.2 channels: the basis of closed-state inactivation.
2008,
Pubmed
England,
A novel K+ channel beta-subunit (hKv beta 1.3) is produced via alternative mRNA splicing.
1995,
Pubmed
,
Xenbase
Fedida,
Gating of voltage-dependent potassium channels.
2001,
Pubmed
Fergus,
Kv channel subunits that contribute to voltage-gated K+ current in renal vascular smooth muscle.
2003,
Pubmed
Ficker,
Molecular determinants of dofetilide block of HERG K+ channels.
1998,
Pubmed
,
Xenbase
Gomez-Lagunas,
Quinidine interaction with Shab K+ channels: pore block and irreversible collapse of the K+ conductance.
2010,
Pubmed
HODGKIN,
A quantitative description of membrane current and its application to conduction and excitation in nerve.
1952,
Pubmed
Hoshi,
Shaker potassium channel gating. I: Transitions near the open state.
1994,
Pubmed
,
Xenbase
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
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
Kerschensteiner,
Heteromeric assembly of Kv2.1 with Kv9.3: effect on the state dependence of inactivation.
1999,
Pubmed
,
Xenbase
Klemic,
Inactivation of Kv2.1 potassium channels.
1998,
Pubmed
,
Xenbase
Klemic,
U-type inactivation of Kv3.1 and Shaker potassium channels.
2001,
Pubmed
,
Xenbase
Kramer,
Modulation of potassium channel gating by coexpression of Kv2.1 with regulatory Kv5.1 or Kv6.1 alpha-subunits.
1998,
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
Loots,
Protein rearrangements underlying slow inactivation of the Shaker K+ channel.
1998,
Pubmed
López-Barneo,
Effects of external cations and mutations in the pore region on C-type inactivation of Shaker potassium channels.
1993,
Pubmed
,
Xenbase
Marom,
State-dependent inactivation of the Kv3 potassium channel.
1994,
Pubmed
,
Xenbase
Morales,
A novel beta subunit increases rate of inactivation of specific voltage-gated potassium channel alpha subunits.
1995,
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
Patlak,
Molecular kinetics of voltage-dependent Na+ channels.
1991,
Pubmed
Qu,
Functional roles of the extracellular segments of the sodium channel alpha subunit in voltage-dependent gating and modulation by beta1 subunits.
1999,
Pubmed
,
Xenbase
Rasmusson,
C-type inactivation controls recovery in a fast inactivating cardiac K+ channel (Kv1.4) expressed in Xenopus oocytes.
1995,
Pubmed
,
Xenbase
Rasmusson,
Inactivation of voltage-gated cardiac K+ channels.
1998,
Pubmed
Rettig,
Inactivation properties of voltage-gated K+ channels altered by presence of beta-subunit.
1994,
Pubmed
,
Xenbase
Sheng,
Subcellular segregation of two A-type K+ channel proteins in rat central neurons.
1992,
Pubmed
,
Xenbase
Tamkun,
Molecular cloning and characterization of two voltage-gated K+ channel cDNAs from human ventricle.
1991,
Pubmed
Todt,
Ultra-slow inactivation in mu1 Na+ channels is produced by a structural rearrangement of the outer vestibule.
1999,
Pubmed
,
Xenbase
Trimmer,
Localization of voltage-gated ion channels in mammalian brain.
2004,
Pubmed
Veh,
Immunohistochemical localization of five members of the Kv1 channel subunits: contrasting subcellular locations and neuron-specific co-localizations in rat brain.
1995,
Pubmed
Wang,
Time- and voltage-dependent components of Kv4.3 inactivation.
2005,
Pubmed
,
Xenbase
Wang,
Kv1.4 channel block by quinidine: evidence for a drug-induced allosteric effect.
2003,
Pubmed
,
Xenbase
Zagotta,
Restoration of inactivation in mutants of Shaker potassium channels by a peptide derived from ShB.
1990,
Pubmed
,
Xenbase
Zhang,
Molecular determinants of voltage-dependent inactivation in calcium channels.
1994,
Pubmed
,
Xenbase
Zhou,
Potassium channel receptor site for the inactivation gate and quaternary amine inhibitors.
2001,
Pubmed
,
Xenbase