Ion channels are responsible for the permeation of ions across the membrane and their central role in cellular physiology is well established. Historically, the direct study of ion channels has been considered technically challenging. As such, a significant barrier to drug discovery for ion channels has been the low throughput of high quality electrophysiological data. The emergence of automated high throughput platforms for studying ion channel kinetics and pharmacology has lowered this barrier. Ion channels are now recognized as increasingly important drug targets and a diverse range of ion channels are implicated in a variety of drug discovery and cardiac safety assessment programs. The TRP (Transient Receptor Potential) superfamily of ion channels play a crucial role in a broad range of sensory functions including vision, taste, olfaction, hearing, touch, pain and thermosensation. Many of the TRP channels are polymodal in their activation and deactivation mechanisms and even with conventional patch clamp electrophysiology, the TRP channels are considered to be a very complex target class. Here we present an update on the significant progress made on the TRP receptor assays with the available automated patch clamp systems.
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http://dx.doi.org/10.1007/978-94-007-0265-3_5 | DOI Listing |
J Agric Food Chem
January 2025
Institute for Neurodegenerative Diseases, University of California, San Francisco, San Francisco, California 94158, United States.
Pesticides, including insecticides, are indispensable for large-scale agriculture. Modulating chloride ion channels has proven highly successful as a mode of action (MoA) for insect management. Identifying new ligands for these channels affords opportunities for the potential development of new insecticide products.
View Article and Find Full Text PDFCNS Neurosci Ther
January 2025
Department of Neurology, Mental and Neurological Disease Research Center, The Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China.
Aims: The aim of this study is to investigate the role of glymphatic function of cerebral autosomal dominant arteriopathy, subcortical infarcts, and leukoencephalopathy (CADASIL), the most common monogenic small vessel disease caused by NOTCH3 mutation, and to explore potential therapeutic strategies to improve glymphatic function.
Methods: We assessed glymphatic influx and efflux function in CADASIL mouse models (Notch3) and correlated these findings with brain atrophy in CADASIL patients. We also investigated the underlying mechanisms of glymphatic impairment, focusing the expression of AQP4 in astrocytic endfeet.
Small
January 2025
Shenzhen Key Laboratory of Energy Materials for Carbon Neutrality, Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences, Shenzhen, 518055, China.
Aqueous zinc-based batteries (AZBs) are gaining widespread attention owing to their intrinsic safety, relatively low electrode potential, and high theoretical capacity. Transition metal dichalcogenides (TMDs) have convenient 2D ion diffusion channels, so they have been identified as promising host materials for AZBs, but face several key challenges such as the narrow interlayer spacing and the lack of in-deep understanding energy storage mechanisms. This review presents a comprehensive summary and discussion of the intrinsic structure, charge storage mechanisms, and key fabrication strategies of TMD-based cathodes for AZBs.
View Article and Find Full Text PDFEur J Immunol
January 2025
Molecular Horizons and School of Chemistry and Molecular Bioscience, University of Wollongong, Wollongong, Australia.
P2X7 is an extracellular adenosine 5'-triphosphate (ATP)-gated cation channel that plays various roles in inflammation and immunity. P2X7 is present on peripheral blood monocytes, dendritic cells (DCs), and innate and adaptive lymphocytes. The anti-human P2X7 monoclonal antibody (mAb; clone L4), used for immunolabelling P2X7 or blocking P2X7 activity, is a murine IgG2 antibody, but its ability to mediate complement-dependent cytotoxicity (CDC) is unknown.
View Article and Find Full Text PDFNephrology (Carlton)
February 2025
Department of Quality Management, Tianjin Blood Center, Tianjin, China.
Aim: To study the effect and elucidate the underlying mechanisms of VDAC1-ΔC on autophagy in renal tubular epithelial cells injured by hypoxia/reoxygenation.
Methods: C57/BL6 mice were randomly divided into groups: sham operation group, IRI 1d group and IRI 2d group. The inner canthal blood of mice was collected to detect the levels of serum creatinine and urea nitrogen and kidney tissues were sampled, and sections were stained with Periodic acid-Schiff for morphological evaluation.
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