We developed a suite of screening assays using manual patch-clamp, automated patch-clamp and fluorescence-based platforms capable of identifying modulators of the TRPML1-4A channel.
We developed a suite of screening assays using manual patch-clamp, automated patch-clamp and fluorescence-based platforms capable of identifying modulators of the TRPML1-4A channel.
Clear decision-making data for your project team is vital to ensure you avoid costly issues related to QTc and QRS cardiac liabilities in the clinic.
Hear from industry experts, Derek Leishman (VP Translational and Quantitative Toxicology, Eli Lilly and Company) and Steve Jenkinson (Metrion).
Jenkinson, Steve Advanced In Vitro Screening of New Drugs for Proarrhythmic Activity, Genetic Engineering News. 2024 44:5, 48-50
Current clamp recordings provide more physiologically relevant measurements of ion channel activity (in comparison to voltage clamp), allowing the contribution of different ion channel sub-types to resting membrane potential to be evaluated.
Gary Stephens, Edwards Stevens (2024) Springer
DOI: 10.1007/978-3-031-52197-3
Eliana is a two-year-old from Canada with a de novo mutation (V434L) in her KCNC1 gene which encodes for the Kv3.1 channel in central nervous system neurons such as cerebellar neurons and GABAergic interneurons. The mutation manifests as a variety of neurological disorders which can include myoclonic epilepsy and ataxia due to K+ channel mutation, developmental epileptic encephalopathy (DEE), or hypotonia, depending on the specific variant. Although Eliana does not exhibit typical DEE, she suffers from hypotonia, cortical-visual impairment, vertical nystagmus, and global delays.
Choi, Dongchana; Goodwin, Georgea; Stevens, Edward B.b; Soliman, Nadiac; Namer, Barbarad,e; Denk, Franziskaa,* (2023) PAIN
DOI: 10.1097/j.pain.0000000000003115
The endo-lysosomal system is a series of intracellular organelles responsible for recycling and degradation of macromolecules. Endo-lysosomes express several functionally diverse ion channels, crucial for regulating organelle trafficking and intracellular signalling as well as maintaining the acidic luminal pH for optimal enzymatic activity. Dysfunctions within the endo-lysosomal system are associated with multiple disorders including lysosomal storage disorders and neurodegenerative diseases such as Alzheimer’s and Parkinson’s disease. Lysosomal ion channels have therefore gained significant attention as potential targets for novel therapeutics.
Lysosomes are a critical component of eukaryotic cells, playing a role in degradation and recycling processes, signal transduction and extracellular secretion(I). Ion channels expressed on the endo-lysosomal membrane are crucial in intracellular signalling and maintaining the acidic luminal pH for optimal hydrolase activity(II). There are a number metabolic disorders, known as lysosomal storage diseases, that arise from lysosomal dysfunction(III).
Nace Zidar a., Tihomir Tomaˇsiˇc., Danijel Kikelj., Martina Durcik., Jan Tytgat., Steve Peigneur., Marc Rogers., Alexander Haworth., and Robert W. Kirby. (2023) New aryl and acylsulfonamides as state-dependent inhibitors of Nav1.3 voltage-gated sodium channel. European Journal of Medicinal Chemistry, 2023.