We have developed a robust high-throughput automated electrophysiology assay using a monoclonal CHO-hNav1.9 cellular reagent suitable for fully supporting a Nav1.9 discovery program.
Hyperpolarisation-activated cyclic nucleotide-gated (HCN) channels are a family of four non-selective cation channels (HCN1-4) that help regulate cardiac and neuronal rhythmicity. The HCN channels, differentially modulated by cyclic nucleotides, phosphorylation and neuromodulators, activate upon membrane hyperpolarisation, conducting inward K+ and Na+ currents to return cells to their resting membrane potential. HCN channel dysfunction has been associated with a range of neurological disorders including epilepsies, Parkinson’s Disease and pain1. Highly expressed in nociceptors, HCN2 has been implicated as a regulator of inflammatory and neuropathic pain. Inflammatory mediators increase neuronal cyclic adenosine monophosphate (cAMP) production, shifting HCN2 activation to more depolarised potentials, increasing the frequency of nociceptor firing. Currently, ivabradine is the only clinically approved HCN blocker used for treatment of chronic angina2. Ivabradine has been shown to reduce both inflammatory and neuropathic pain sensitivity in mouse models through reduced firing of peripheral nociceptors3. These findings highlight HCN2 as a potential nonopioid
drug target in the treatment of chronic inflammatory and neuropathic pain.
Here, we demonstrate the generation and validation of a stable CHO-hHCN2 cell line used as a cellular tool in the successful development of hHCN2 automated electrophysiology screening assays. These assays create a platform for the screening of novel compounds to advance the development of selective hHCN2 modulators, useful in the treatment of pain.
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We have developed a robust high-throughput automated electrophysiology assay using a monoclonal CHO-hNav1.9 cellular reagent suitable for fully supporting a Nav1.9 discovery program.
Metrion and Sophion present findings that determine whether other insoluble salts can act as seal enhancers and how these solution pairs affect the biophysical properties and pharmacology of the investigated ion channels.