Use of cultured human neuroblastoma cells in rapid discovery of the voltage-gated potassium-channel blockers.

J Pharm Pharmacol

CV/CNS Research Section, American Cyanamid Company, Lederle Laboratories, Pearl River, New York 10965.

Published: September 1994

Depolarization of human neuroblastoma cells by high concentrations of extracellular potassium ions, leads to the activation of the voltage-gated potassium channels. The activity of such potassium channels can be effectively and rapidly monitored by tracking the efflux of 86Rb from pre-loaded target cells in response to the depolarizing stimulus. The inclusion of compounds with unknown activity in the assay medium, can result in the identification of novel blockers of the voltage-gated potassium channels. Since this functional assay is performed in 96-well microtitre plates, it represents a rapid and high-volume primary screening method for the detection and identification of the voltage-gated potassium-channel blockers, which may have therapeutic utility in several indications including memory degeneration and cardiac arrhythmias.

Download full-text PDF

Source
http://dx.doi.org/10.1111/j.2042-7158.1994.tb03892.xDOI Listing

Publication Analysis

Top Keywords

potassium channels
12
human neuroblastoma
8
neuroblastoma cells
8
voltage-gated potassium-channel
8
potassium-channel blockers
8
voltage-gated potassium
8
cultured human
4
cells rapid
4
rapid discovery
4
voltage-gated
4

Similar Publications

The Kv3.2 subfamily of voltage activated potassium channels encoded by the gene is abundantly expressed in neurons that fire trains of fast action potentials that are a major source of cortical inhibition. Gain-of-function (GOF) pathogenic variants in and , encoding Kv3.

View Article and Find Full Text PDF

The hypoglycemic effects of nateglinide (NTG) were examined in rats with acute peripheral inflammation (API) induced by carrageenan treatment, and the mechanisms accounting for altered hypoglycemic effects were investigated. NTG was administered through the femoral vein in control and API rats, and its plasma concentration profile was characterized. The time courses of the changes in plasma glucose and insulin levels were also examined.

View Article and Find Full Text PDF

Kappa opioid receptors (KOR) expressed by peripheral pain-sensing neurons (nociceptors) are a promising target for development of effective and safer analgesics for inflammatory pain that are devoid of central nervous system adverse effects. Here we sought to delineate the signaling pathways that underlie peripheral KOR-mediated antinociception in adult male and female Sprague-Dawley rats. In an inflammatory model of pain, local intraplantar (i.

View Article and Find Full Text PDF

The Shab family potassium channels are highly enriched at the presynaptic terminals of human neurons.

J Biol Chem

January 2025

Biochemistry & Molecular Biology, Colorado State University, Fort Collins, CO 80523, USA; Molecular, Cellular & Integrated Neurosciences, Colorado State University, Fort Collins, CO 80523, USA; Cell & Molecular Biology, Colorado State University, Fort Collins, CO 80523, USA. Electronic address:

The Shab family voltage-gated K channels (i.e., Kv2.

View Article and Find Full Text PDF

The NMDAR-BK channelosomes as regulators of synaptic plasticity.

Biochem Soc Trans

January 2025

Departamento de Ciencias Médicas Básicas, Facultad de Ciencias de la Salud-sección Medicina, Universidad de La Laguna, Tenerife, ES-38071, Spain.

Large conductance voltage- and calcium-activated potassium channels (BK channels) are extensively found throughout the central nervous system and play a crucial role in various neuronal functions. These channels are activated by a combination of cell membrane depolarisation and an increase in intracellular calcium concentration, provided by calcium sources located close to BK. In 2001, Isaacson and Murphy first demonstrated the coupling of BK channels with N-methyl-D-aspartate receptors (NMDAR) in olfactory bulb neurons.

View Article and Find Full Text PDF

Want AI Summaries of new PubMed Abstracts delivered to your In-box?

Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!