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.
Inhibition of the K+ channel kv1.4 by acidosis: protonation of an extracellular histidine slows the recovery from N-type inactivation.
Claydon TW
,
Boyett MR
,
Sivaprasadarao A
,
Ishii K
,
Owen JM
,
O'Beirne HA
,
Leach R
,
Komukai K
,
Orchard CH
.
???displayArticle.abstract???
1. Acidosis alters the transient outward current, ito, in the heart. We have studied the mechanism underlying the effect of acidosis on one of the K+ channels, Kv1.4 (heterologously expressed in Xenopus laevis oocytes), known to underlie ito. 2. At pH 6.5, wild-type Kv1.4 current was inhibited during repetitive pulsing, in part as a result of a slowing of recovery from N-type inactivation. 3. Acidosis still caused slowing of recovery after deletion of just one (either the first or second) of the N-terminal inactivation ball domains. However, deletion of both the N-terminal inactivation ball domains greatly reduced the inhibition. 4. As well as the N-terminus, other parts of the channel are also required for the effect of acidosis, because, whereas the transfer of the N-terminus of Kv1.4 to Kv1.2 conferred N-type inactivation, it did not confer acidosis sensitivity. 5. Replacement of an extracellular histidine with a glutamine residue (H508Q) abolished the slowing of recovery by acidosis. Reduction of C-type inactivation by raising the bathing K+ concentration or by the mutation K532Y also abolished the slowing. 6. It is concluded that binding of protons to H508 enhances C-type inactivation and this causes a slowing of recovery from N-type inactivation and, thus, an inhibition of current during repetitive pulsing.
Barry,
Functional knockout of the transient outward current, long-QT syndrome, and cardiac remodeling in mice expressing a dominant-negative Kv4 alpha subunit.
1998, Pubmed
Barry,
Functional knockout of the transient outward current, long-QT syndrome, and cardiac remodeling in mice expressing a dominant-negative Kv4 alpha subunit.
1998,
Pubmed
Brahmajothi,
Distinct transient outward potassium current (Ito) phenotypes and distribution of fast-inactivating potassium channel alpha subunits in ferret left ventricular myocytes.
1999,
Pubmed
Comer,
Cloning and characterization of an Ito-like potassium channel from ferret ventricle.
1994,
Pubmed
,
Xenbase
Fiset,
Shal-type channels contribute to the Ca2+-independent transient outward K+ current in rat ventricle.
1997,
Pubmed
Guo,
Regulation of Kv4.2 and Kv1.4 K+ channel expression by myocardial hypertrophic factors in cultured newborn rat ventricular cells.
1998,
Pubmed
Guo,
Molecular basis of transient outward K+ current diversity in mouse ventricular myocytes.
1999,
Pubmed
Hulme,
Effect of acidosis on transient outward potassium current in isolated rat ventricular myocytes.
2000,
Pubmed
Johns,
Suppression of neuronal and cardiac transient outward currents by viral gene transfer of dominant-negative Kv4.2 constructs.
1997,
Pubmed
Kondoh,
A mammalian transient type K+ channel, rat Kv1.4, has two potential domains that could produce rapid inactivation.
1997,
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
Mikaelian,
Modification of the overlap extension method for extensive mutagenesis on the same template.
1996,
Pubmed
Pérez-Cornejo,
H+ ion modulation of C-type inactivation of Shaker K+ channels.
1999,
Pubmed
Rasmusson,
C-type inactivation controls recovery in a fast inactivating cardiac K+ channel (Kv1.4) expressed in Xenopus oocytes.
1995,
Pubmed
,
Xenbase
Sasaki,
Regulation mechanisms of intracellular pH of Xenopus laevis oocyte.
1992,
Pubmed
,
Xenbase
Steidl,
Differential sensitivity of voltage-gated potassium channels Kv1.5 and Kv1.2 to acidic pH and molecular identification of pH sensor.
1999,
Pubmed
,
Xenbase
Stengl,
Modulation of transient outward current by extracellular protons and Cd2+ in rat and human ventricular myocytes.
1998,
Pubmed
Wang,
Potential molecular basis of different physiological properties of the transient outward K+ current in rabbit and human atrial myocytes.
1999,
Pubmed
,
Xenbase
Wickenden,
Regional contributions of Kv1.4, Kv4.2, and Kv4.3 to transient outward K+ current in rat ventricle.
1999,
Pubmed
Xu,
Four kinetically distinct depolarization-activated K+ currents in adult mouse ventricular myocytes.
1999,
Pubmed
Xu,
Developmental analysis reveals mismatches in the expression of K+ channel alpha subunits and voltage-gated K+ channel currents in rat ventricular myocytes.
1996,
Pubmed
