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.
???displayArticle.abstract???
Niflumic acid [2-((3-(trifluoromethyl)phenyl)amino)-3-pyridinecarboxylic acid, NFA] is a nonsteroidal anti-inflammatory drug that also blocks or modulates the gating of a wide spectrum of ion channels. Here we investigated the mechanism of channel activation by NFA on ether-a-go-go-related gene (ERG) K(+) channel subtypes expressed in Xenopus laevis oocytes using two-electrode voltage-clamp techniques. NFA acted from the extracellular side of the membrane to differentially enhance ERG channel currents independent of channel state. At 1 mM, NFA shifted the half-point for activation by -6, -18, and -11 mV for ERG1, ERG2, and ERG3 channels, respectively. The half-point for channel inactivation was shifted by +5 to +9 mV by NFA. The structural basis for the ERG subtype-specific response to NFA was explored with chimeric channels and site-directed mutagenesis. The molecular determinants of enhanced sensitivity of ERG2 channels to NFA were isolated to an Arg and a Thr triplet in the extracellular S3-S4 linker.
Busch,
Positive regulation by chloride channel blockers of IsK channels expressed in Xenopus oocytes.
1994, Pubmed,
Xenbase
Busch,
Positive regulation by chloride channel blockers of IsK channels expressed in Xenopus oocytes.
1994,
Pubmed
,
Xenbase Casis,
Mechanism of action of a novel human ether-a-go-go-related gene channel activator.
2006,
Pubmed
,
Xenbase Chiesa,
A novel role for HERG K+ channels: spike-frequency adaptation.
1997,
Pubmed Elmedyb,
Activation of ERG2 potassium channels by the diphenylurea NS1643.
2007,
Pubmed
,
Xenbase Gullo,
ERG K+ channel blockade enhances firing and epinephrine secretion in rat chromaffin cells: the missing link to LQT2-related sudden death?
2003,
Pubmed Hansen,
Activation of human ether-a-go-go-related gene potassium channels by the diphenylurea 1,3-bis-(2-hydroxy-5-trifluoromethyl-phenyl)-urea (NS1643).
2006,
Pubmed
,
Xenbase Kang,
Discovery of a small molecule activator of the human ether-a-go-go-related gene (HERG) cardiac K+ channel.
2005,
Pubmed Lee,
Inhibition of hKv2.1, a major human neuronal voltage-gated K+ channel, by meclofenamic acid.
1999,
Pubmed Liantonio,
Activation and inhibition of kidney CLC-K chloride channels by fenamates.
2006,
Pubmed
,
Xenbase Lu,
Effects of premature stimulation on HERG K(+) channels.
2001,
Pubmed Malykhina,
Fenamate-induced enhancement of heterologously expressed HERG currents in Xenopus oocytes.
2002,
Pubmed
,
Xenbase Mathur,
Role of the S3-S4 linker in Shaker potassium channel activation.
1997,
Pubmed
,
Xenbase Ottolia,
Potentiation of large conductance KCa channels by niflumic, flufenamic, and mefenamic acids.
1994,
Pubmed Peretz,
Meclofenamic acid and diclofenac, novel templates of KCNQ2/Q3 potassium channel openers, depress cortical neuron activity and exhibit anticonvulsant properties.
2005,
Pubmed Rosati,
Glucose- and arginine-induced insulin secretion by human pancreatic beta-cells: the role of HERG K(+) channels in firing and release.
2000,
Pubmed Sacco,
Functional roles of an ERG current isolated in cerebellar Purkinje neurons.
2003,
Pubmed Sanguinetti,
A mechanistic link between an inherited and an acquired cardiac arrhythmia: HERG encodes the IKr potassium channel.
1995,
Pubmed
,
Xenbase Schwarz,
Functions of erg K+ channels in excitable cells.
2004,
Pubmed Scott-Ward,
Direct block of the cystic fibrosis transmembrane conductance regulator Cl(-) channel by niflumic acid.
2004,
Pubmed Shi,
Identification of two nervous system-specific members of the erg potassium channel gene family.
1997,
Pubmed
,
Xenbase 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 Stühmer,
Electrophysiological recording from Xenopus oocytes.
1992,
Pubmed
,
Xenbase Trudeau,
HERG, a human inward rectifier in the voltage-gated potassium channel family.
1995,
Pubmed Wang,
Unexpected and differential effects of Cl- channel blockers on the Kv4.3 and Kv4.2 K+ channels. Implications for the study of the I(to2) current.
1997,
Pubmed
,
Xenbase White,
Niflumic and flufenamic acids are potent reversible blockers of Ca2(+)-activated Cl- channels in Xenopus oocytes.
1990,
Pubmed
,
Xenbase Zhou,
Novel potent human ether-a-go-go-related gene (hERG) potassium channel enhancers and their in vitro antiarrhythmic activity.
2005,
Pubmed
