KV3.1 is a voltage-gated potassium channel encoded by the KCNC1 gene. Mutations in the KV3.1 protein can manifest as a variety of neurological disorders including myoclonic epilepsy and ataxia due to K+ channel mutation (MEAK), developmental epileptic encephalopathy (DEE), or hypotonia.

Derek J. Leishman, Jessica Brimecombe, William Crumb, Simon Hebeisen, Steve Jenkinson, Peter J. Kilfoil, Hiroshi Matsukawa, Karim Melliti, Yusheng Qu, Journal of Pharmacological and Toxicological Methods, Volume 128, 2024, 107524, ISSN 1056-8719. DOI: 10.1007/978-3-031-52197-3

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The development and validation of electrophysiological assays to study TRPML1 is important to understand the function and pharmacology of the channel. We used a TRPML1 variant that lacks the endo-lysosomal retention sequences (TRPML1-4A), enabling the channel to express at the plasma membrane3. As such channel behaviour can be characterised by means of whole-cell patch-clamp and fluorescence-based techniques.

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