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.
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Front Pharmacol
January 2025
Department of Neuroscience, Washington University in St. Louis, St. Louis, MO, United States.
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 PDFBiol Pharm Bull
January 2025
Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, Okayama 700-8558, Japan.
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 PDFNeuropharmacology
January 2025
Department of Pharmacology, University of Texas Health Science Center at San Antonio, San Antonio, Texas, 78229, USA. Electronic address:
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 PDFJ 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 PDFBiochem 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.
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