We developed a high-throughput, electrophysiological assay of TREK-1 function to identify novel modulators. The assay was optimized to identify both activators and inhibitors, providing comprehensive mechanistic data for high value, limited supply screening libraries, such as the venom fraction library used in this study (Targeted Venom Discovery Array, T-VDA, Venomtech, UK).

Highly specialised and tailored neuronal assays for pharmacological screening.

Reliably evaluate the proarrhythmic and cardiotoxic liabilities of your compounds.

Specialist ion channel screening to accelerate early-stage screening and lead optimisation.

We report the development and optimisation of a TREK-1 functional assay using the Qube 384, an automated patch clamp platform capable of supporting high-throughput screening. The assay was optimized to identify both activators and inhibitors on the same plate, providing key mechanistic data for high value, limited supply screening libraries such as venom fractions used in this study (Targeted Venom Discovery Array, TVDA, Venomtech, UK).

Scientifica’s PatchScope Pro is an integrated electrophysiology rig incorporating an inverted phase-contrast fluorescence microscope, motorised XY stage and PatchStar micromanipulators, suitable for patch-clamp recording.

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.

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).