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.
State-dependent barium block of wild-type and inactivation-deficient HERG channels in Xenopus oocytes.
Weerapura M, Nattel S, Courtemanche M, Doern D, Ethier N, Hebert T.
???displayArticle.abstract???
The effects of Ba2+ on current resulting from the heterologous expression of the human ether-à-go-go related gene (HERG) (IHERG) was studied with two-electrode voltage clamp techniques in Xenopus oocytes. Ba2+ produced time- and voltage-dependent block of IHERG. Significant inhibition was seen at concentrations as low as 1 microM. Inhibition was greatest at step potentials between -40 and 0 mV; at more positive potentials, inhibition decreased in association with time-dependent unblocking of channels. An inactivation-attenuated mutant of HERG (S631A) was prepared and expressed in Xenopus oocytes. Ba2+ block of S631A differed from that of HERG in that extensive unblocking was no longer seen at positive potentials and the voltage dependence of step current block was greatly attenuated. A mathematical model was applied to analyse quantitatively the inhibitory effects of Ba2+ on IHERG. The model suggested similar voltage-dependent affinity of Ba2+ for the open and closed states, along with absence of binding to the inactivated state, and accounted well for Ba2+ effects on both wild-type and S631A channels. We conclude that Ba2+ potently inhibits IHERG in a characteristic state-dependent fashion, with strong unblocking at positive potentials related to the presence of an intact C-type inactivation mechanism.
Abbott,
MiRP1 forms IKr potassium channels with HERG and is associated with cardiac arrhythmia.
1999, Pubmed,
Xenbase
Abbott,
MiRP1 forms IKr potassium channels with HERG and is associated with cardiac arrhythmia.
1999,
Pubmed
,
Xenbase Anumonwo,
Delayed rectification in single cells isolated from guinea pig sinoatrial node.
1992,
Pubmed Armstrong,
Block of squid axon K channels by internally and externally applied barium ions.
1982,
Pubmed Balser,
Time-dependent outward current in guinea pig ventricular myocytes. Gating kinetics of the delayed rectifier.
1990,
Pubmed Barhanin,
K(V)LQT1 and lsK (minK) proteins associate to form the I(Ks) cardiac potassium current.
1996,
Pubmed
,
Xenbase Barry,
Myocardial potassium channels: electrophysiological and molecular diversity.
1996,
Pubmed Basso,
Pore accessibility during C-type inactivation in Shaker K+ channels.
1998,
Pubmed Berthet,
C-terminal HERG mutations: the role of hypokalemia and a KCNQ1-associated mutation in cardiac event occurrence.
1999,
Pubmed Brochu,
Pacemaker current in single cells and in aggregates of cells dissociated from the embryonic chick heart.
1992,
Pubmed Carmeliet,
Characterization of the acetylcholine-induced potassium current in rabbit cardiac Purkinje fibres.
1986,
Pubmed Colatsky,
Channel specificity in antiarrhythmic drug action. Mechanism of potassium channel block and its role in suppressing and aggravating cardiac arrhythmias.
1990,
Pubmed Curran,
A molecular basis for cardiac arrhythmia: HERG mutations cause long QT syndrome.
1995,
Pubmed DiFrancesco,
Barium-induced blockade of the inward rectifier in calf Purkinje fibres.
1984,
Pubmed Eaton,
Effects of barium on the potassium conductance of squid axon.
1980,
Pubmed Fermini,
Removal of sialic acid alters both T- and L-type calcium currents in cardiac myocytes.
1991,
Pubmed Ficker,
Molecular determinants of dofetilide block of HERG K+ channels.
1998,
Pubmed
,
Xenbase Giles,
Voltage clamp of bull-frog cardiac pace-maker cells: a quantitative analysis of potassium currents.
1985,
Pubmed Gillis,
The effects of barium, dofetilide and 4-aminopyridine (4-AP) on ventricular repolarization in normal and hypertrophied rabbit heart.
1998,
Pubmed Harris,
A permanent ion binding site located between two gates of the Shaker K+ channel.
1998,
Pubmed
,
Xenbase Hebert,
Voltage dependencies of the fast and slow gating modes of RIIA sodium channels.
1994,
Pubmed
,
Xenbase Ho,
Blockade of HERG channels expressed in Xenopus laevis oocytes by external divalent cations.
1999,
Pubmed
,
Xenbase Ho,
Voltage-dependent blockade of HERG channels expressed in Xenopus oocytes by external Ca2+ and Mg2+.
1998,
Pubmed
,
Xenbase Hurst,
External barium block of Shaker potassium channels: evidence for two binding sites.
1995,
Pubmed
,
Xenbase Hurst,
Molecular determinants of external barium block in Shaker potassium channels.
1996,
Pubmed
,
Xenbase Kiehn,
Molecular physiology and pharmacology of HERG. Single-channel currents and block by dofetilide.
1996,
Pubmed
,
Xenbase Li,
Evidence for two components of delayed rectifier K+ current in human ventricular myocytes.
1996,
Pubmed Miller,
Coupling of voltage-dependent gating and Ba++ block in the high-conductance, Ca++-activated K+ channel.
1987,
Pubmed Noble,
Outward membrane currents activated in the plateau range of potentials in cardiac Purkinje fibres.
1969,
Pubmed Paquette,
Effects of divalent cations on the E-4031-sensitive repolarization current, I(Kr), in rabbit ventricular myocytes.
1998,
Pubmed Sanguinetti,
Delayed rectifier outward K+ current is composed of two currents in guinea pig atrial cells.
1991,
Pubmed Sanguinetti,
Coassembly of K(V)LQT1 and minK (IsK) proteins to form cardiac I(Ks) potassium channel.
1996,
Pubmed
,
Xenbase 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 Shimoni,
Role of an inwardly rectifying potassium current in rabbit ventricular action potential.
1992,
Pubmed Smith,
The inward rectification mechanism of the HERG cardiac potassium channel.
1996,
Pubmed Spector,
Fast inactivation causes rectification of the IKr channel.
1996,
Pubmed
,
Xenbase Taglialatela,
Barium blockade of a clonal potassium channel and its regulation by a critical pore residue.
1993,
Pubmed
,
Xenbase Trudeau,
HERG, a human inward rectifier in the voltage-gated potassium channel family.
1995,
Pubmed Wang,
Positional cloning of a novel potassium channel gene: KVLQT1 mutations cause cardiac arrhythmias.
1996,
Pubmed Wang,
Modulation of HERG affinity for E-4031 by [K+]o and C-type inactivation.
1997,
Pubmed
,
Xenbase Wang,
A quantitative analysis of the activation and inactivation kinetics of HERG expressed in Xenopus oocytes.
1997,
Pubmed
,
Xenbase WERMAN,
Graded and all-or-none electrogenesis in arthropod muscle. II. The effects of alkali-earth and onium ions on lobster muscle fibers.
1961,
Pubmed Zang,
Barium block of the muscarinic potassium current in guinea-pig atrial cells.
1995,
Pubmed Zou,
Single HERG delayed rectifier K+ channels expressed in Xenopus oocytes.
1997,
Pubmed
,
Xenbase Zou,
A mutation in the pore region of HERG K+ channels expressed in Xenopus oocytes reduces rectification by shifting the voltage dependence of inactivation.
1998,
Pubmed
,
Xenbase
