"Ion Channels and Neuropharmacology: From the Past to the Future" is the main theme of articles in Volume 60 of the . Reviews in this volume discuss a wide spectrum of therapeutically relevant ion channels and GPCRs with a particular emphasis on structural studies that elucidate drug binding sites and mechanisms of action. The regulation of ion channels by second messengers, including Ca and cyclic AMP, and lipid mediators is also highly relevant to several of the ion channels discussed, including KCNQ channels, HCN channels, L-type Ca channels, and AMPA receptors, as well as the aquaporin channels. Molecular identification of exactly where drugs bind in the structure not only elucidates their mechanism of action but also aids future structure-based drug discovery efforts to focus on relevant pharmacophores. The ion channels discussed here are targets for multiple nervous system diseases, including epilepsy and neuropathic pain. This theme complements several previous themes, including "New Therapeutic Targets," "New Approaches for Studying Drug and Toxicant Action: Applications to Drug Discovery and Development," and "New Methods and Novel Therapeutic Approaches in Pharmacology and Toxicology."
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http://dx.doi.org/10.1146/annurev-pharmtox-082719-110050 | DOI Listing |
J Gen Physiol
March 2025
Institute for Neurophysiology, Uniklinik RWTH Aachen University, Aachen, Germany.
Voltage-gated sodium channels (VGSCs) in the peripheral nervous system shape action potentials (APs) and thereby support the detection of sensory stimuli. Most of the nine mammalian VGSC subtypes are expressed in nociceptors, but predominantly, three are linked to several human pain syndromes: while Nav1.7 is suggested to be a (sub-)threshold channel, Nav1.
View Article and Find Full Text PDFProc Natl Acad Sci U S A
January 2025
Department of Neurology, Yale School of Medicine, New Haven, CT 06520.
Pain impacts billions of people worldwide, but treatment options are limited and have a spectrum of adverse effects. The search for safe and nonaddictive pain treatments has led to a focus on key mediators of nociceptor excitability. Voltage-gated sodium (Nav) channels in the peripheral nervous system-Nav1.
View Article and Find Full Text PDFFront Pharmacol
January 2025
IDiBE-Instituto de Investigación, Desarrollo e Innovación en Biotecnología Sanitaria de Elche, Universidad Miguel Hernández, Elche, Spain.
The Selectivity Filter (SF) in tetrameric K channels, has a highly conserved sequence, TVGYG, at the extracellular entry to the channel pore region. There, the backbone carbonyl oxygens from the SF residues, create a stack of K binding sites where dehydrated K binds to induce a conductive conformation of the SF. This increases intersubunit interactions and confers a higher stability to the channel against thermal denaturation.
View Article and Find Full Text PDFCNS Neurosci Ther
January 2025
Department of Neurology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, China.
Background: Lysosome is a highly heterogeneous membranous organelle in eukaryotic cells, which regulates many physiological processes in the cell. Studies have found that lysosomal dysfunction disrupts cellular homeostasis and is associated with Parkinson's disease (PD). Transmembrane protein 175 (TMEM175) is a lysosomal cation channel whose activity is essential for lysosomal homeostasis.
View Article and Find Full Text PDFChem Biol Drug Des
January 2025
College of Pharmacology Sciences, Zhejiang University of Technology, Hangzhou, People's Republic of China.
Depression is a mental health disorder and is the fourth most prevalent disease. Previous studies have suggested that statins are involved in the reduction of neuroinflammation. However, the potential mechanism for this relationship is unclear.
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