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 KCNC1 Foundation was founded by the parents of Eliana, a child from Canada who was diagnosed with an ultra-rare de novo mutation (V434L) in the KCNC1 gene, which encodes the KV3.1 ion channel in humans, at age 9 months. Eliana does not display typical DEE, but exhibits significant hypotonia, cortical-visual impairment, vertical nystagmus, and global delays. The KCNC1 Foundation has registered 36 patients affected by 14 different genetic variants in the KCNC1 gene. Of these patients, 25% share the A421V variant, 12.5% have MEAK caused by the R320H variant, a few exhibit the V432M variant, and the remaining variants are seen in 1 – 3 patients.
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).
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.