Analysis of plasma membrane integrity by fluorescent detection of Tl(+) uptake.
AuthorsBowman AM, Nesin OM, Pakhomova ON, Pakhomov AG,
JournalJ Membr Biol
PubMed ID20623351
'The exclusion of polar dyes by healthy cells is widely employed as a simple and reliable test for cell membrane integrity. However, commonly used dyes (propidium, Yo-Pro-1, trypan blue) cannot detect membrane defects which are smaller than the dye molecule itself, such as nanopores that form by exposure to ultrashort ... More
The Ste20 kinases Ste20-related proline-alanine-rich kinase and oxidative-stress response 1 regulate NKCC1 function in sensory neurons.
AuthorsGeng Y, Hoke A, Delpire E,
JournalJ Biol Chem
PubMed ID19307180
'NKCC1 is highly expressed in dorsal root ganglion neurons, where it is involved in gating sensory information. In a recent study, it was shown that peripheral nerve injury results in increased NKCC1 activity, not due to an increase in cotransporter expression, but to increased phosphorylation of the cotransporter (Pieraut, S., ... More
Lipid nanopores can form a stable, ion channel-like conduction pathway in cell membrane.
AuthorsPakhomov AG, Bowman AM, Ibey BL, Andre FM, Pakhomova ON, Schoenbach KH,
JournalBiochem Biophys Res Commun
PubMed ID19450553
Cell permeabilization by electric pulses (EPs), or electroporation, has been well established as a tool to indiscriminately increase membrane flows of water solutes down the concentration and voltage gradients. However, we found that EPs of nanosecond duration (nsEPs) trigger formation of voltage-sensitive and inward-rectifying membrane pores. NsEP-treated cells remain mostly ... More
An ion channel library for drug discovery and safety screening on automated platforms.
AuthorsWible BA, Kuryshev YA, Smith SS, Liu Z, Brown AM,
JournalAssay Drug Dev Technol
PubMed ID19090691
Ion channels represent the third largest class of targets in drug discovery after G-protein coupled receptors and kinases. In spite of this ranking, ion channels continue to be under exploited as drug targets compared with the other two groups for several reasons. First, with 400 ion channel genes and an ... More
A new homogeneous high-throughput screening assay for profiling compound activity on the human ether-a-go-go-related gene channel.
AuthorsTitus SA, Beacham D, Shahane SA, Southall N, Xia M, Huang R, Hooten E, Zhao Y, Shou L, Austin CP, Zheng W,
JournalAnal Biochem
PubMed ID19583963
Long QT syndrome, either inherited or acquired from drug treatments, can result in ventricular arrhythmia (torsade de pointes) and sudden death. Human ether-a-go-go-related gene (hERG) channel inhibition by drugs is now recognized as a common reason for the acquired form of long QT syndrome. It has been reported that more ... More
Cell-based potassium ion channel screening using the FluxOR assay.
AuthorsBeacham DW, Blackmer T, O' Grady M, Hanson GT,
JournalJ Biomol Screen
PubMed ID20208034
FluxOR technology is a cell-based assay used for high-throughput screening measurements of potassium channel activity. Using thallium influx as a surrogate indicator of potassium ion channel activity, the FluxOR Potassium Ion Channel Assay is based on the activation of a novel fluorescent dye. This indicator reports channel activity with a ... More
A thallium-sensitive, fluorescence-based assay for detecting and characterizing potassium channel modulators in mammalian cells.
Potassium channels have been identified as targets for a large number of therapeutic indications. The ability to use a high-throughput functional assay for the detection and characterization of small-molecule modulators of potassium channels is very desirable. However, present techniques capable of screening very large chemical libraries are limited in terms ... More
Molecular architecture of potassium chloride co-transporter KCC2.
Authors
JournalSci Rep
PubMed ID29184062
Selective inhibition of the K(ir)2 family of inward rectifier potassium channels by a small molecule probe: the discovery, SAR, and pharmacological characterization of ML133.
Authors
JournalACS Chem Biol
PubMed ID21615117
The small molecule CLP257 does not modify activity of the K+-Cl- co-transporter KCC2 but does potentiate GABAA receptor activity.
Authors
JournalNat Med
PubMed ID29216042
Kv1.5 channel mediates monosodium urate-induced activation of NLRP3 inflammasome in macrophages and arrhythmogenic effects of urate on cardiomyocytes.
Authors
JournalMol Biol Rep
PubMed ID35368226
Identification of human Ether-à-go-go related gene modulators by three screening platforms in an academic drug-discovery setting.