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.
A mutation in the pore region of HERG K+ channels expressed in Xenopus oocytes reduces rectification by shifting the voltage dependence of inactivation.
Zou A
,
Xu QP
,
Sanguinetti MC
.
???displayArticle.abstract???
1. The effects of a mutation in the human ether-a-go-go-related gene (HERG) (Ser631 to Ala, S631A) on the voltage- and extracellular [K+] dependence of inactivation were studied in Xenopus oocytes using two microelectrode and single channel voltage-clamp techniques. 2. The voltage required for half-inactivation of S631A HERG was 102 mV more positive than for wild-type (WT)-HERG, resulting in reduced rectification of the steady-state current-voltage relationship. In contrast, the voltage dependence of channel activation was not altered by the S631A mutation. These findings indicate that inactivation of HERG channels is not linked to activation. 3. Rectification of whole-cell S631A HERG current was caused by a voltage-dependent reduction in open probability, and inward rectification of the current-voltage relationship of single channels. 4. Elevation of extracellular [K+] from 2 to 20 mM shifted the half-point for inactivation by +20 mV for WT-HERG, and +25 mV for S631A HERG. Thus, elevated [K+]o and the S631A mutation affect HERG inactivation by different mechanisms. 5. The S631A mutation altered the ion translocation rate of HERG channels. The single channel conductance (gamma) of S631A HERG was 20 pS between -40 and-100 mV, and 6.0 pS between +40 and +100 mV (120 mM extracellular K+). This compares to a gamma of 12.1 and 5.1 pS for WT-HERG channels under the same conditions.
Baukrowitz,
Modulation of K+ current by frequency and external [K+]: a tale of two inactivation mechanisms.
1995, Pubmed
Baukrowitz,
Modulation of K+ current by frequency and external [K+]: a tale of two inactivation mechanisms.
1995,
Pubmed
Choi,
Tetraethylammonium blockade distinguishes two inactivation mechanisms in voltage-activated K+ channels.
1991,
Pubmed
Curran,
A molecular basis for cardiac arrhythmia: HERG mutations cause long QT syndrome.
1995,
Pubmed
Demo,
The inactivation gate of the Shaker K+ channel behaves like an open-channel blocker.
1991,
Pubmed
Fakler,
Strong voltage-dependent inward rectification of inward rectifier K+ channels is caused by intracellular spermine.
1995,
Pubmed
,
Xenbase
Ficker,
Spermine and spermidine as gating molecules for inward rectifier K+ channels.
1994,
Pubmed
,
Xenbase
Heginbotham,
The aromatic binding site for tetraethylammonium ion on potassium channels.
1992,
Pubmed
Horie,
Two types of delayed rectifying K+ channels in atrial cells of guinea pig heart.
1990,
Pubmed
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
Ito,
A rapidly activating delayed rectifier K+ channel in rabbit sinoatrial node cells.
1995,
Pubmed
Kirsch,
Differences between the deep pores of K+ channels determined by an interacting pair of nonpolar amino acids.
1992,
Pubmed
,
Xenbase
Liu,
Activation and inactivation kinetics of an E-4031-sensitive current from single ferret atrial myocytes.
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
Lu,
Electrostatic tuning of Mg2+ affinity in an inward-rectifier K+ channel.
1994,
Pubmed
,
Xenbase
Pardo,
Extracellular K+ specifically modulates a rat brain K+ channel.
1992,
Pubmed
,
Xenbase
Rasmusson,
C-type inactivation controls recovery in a fast inactivating cardiac K+ channel (Kv1.4) expressed in Xenopus oocytes.
1995,
Pubmed
,
Xenbase
Roden,
Multiple mechanisms in the long-QT syndrome. Current knowledge, gaps, and future directions. The SADS Foundation Task Force on LQTS.
1996,
Pubmed
Sanguinetti,
A mechanistic link between an inherited and an acquired cardiac arrhythmia: HERG encodes the IKr potassium channel.
1995,
Pubmed
,
Xenbase
Sanguinetti,
Two components of cardiac delayed rectifier K+ current. Differential sensitivity to block by class III antiarrhythmic agents.
1990,
Pubmed
Schönherr,
Molecular determinants for activation and inactivation of HERG, a human inward rectifier potassium channel.
1996,
Pubmed
,
Xenbase
Shibasaki,
Conductance and kinetics of delayed rectifier potassium channels in nodal cells of the rabbit heart.
1987,
Pubmed
Smith,
The inward rectification mechanism of the HERG cardiac potassium channel.
1996,
Pubmed
Snyders,
High affinity open channel block by dofetilide of HERG expressed in a human cell line.
1996,
Pubmed
,
Xenbase
Spector,
Class III antiarrhythmic drugs block HERG, a human cardiac delayed rectifier K+ channel. Open-channel block by methanesulfonanilides.
1996,
Pubmed
,
Xenbase
Spector,
Fast inactivation causes rectification of the IKr channel.
1996,
Pubmed
,
Xenbase
Trudeau,
HERG, a human inward rectifier in the voltage-gated potassium channel family.
1995,
Pubmed
Veldkamp,
Delayed rectifier channels in human ventricular myocytes.
1995,
Pubmed
Wang,
Time, voltage and ionic concentration dependence of rectification of h-erg expressed in Xenopus oocytes.
1996,
Pubmed
,
Xenbase
Wang,
A quantitative analysis of the activation and inactivation kinetics of HERG expressed in Xenopus oocytes.
1997,
Pubmed
,
Xenbase
Wible,
Gating of inwardly rectifying K+ channels localized to a single negatively charged residue.
1994,
Pubmed
,
Xenbase
Yang,
Rapid inactivation determines the rectification and [K+]o dependence of the rapid component of the delayed rectifier K+ current in cardiac cells.
1997,
Pubmed
Yellen,
An engineered cysteine in the external mouth of a K+ channel allows inactivation to be modulated by metal binding.
1994,
Pubmed
Zou,
Single HERG delayed rectifier K+ channels expressed in Xenopus oocytes.
1997,
Pubmed
,
Xenbase
