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.
Voltage-dependent sodium channels (Nav) are implicated in a wide range of diseases, with their role in triggering and modulating membrane excitability making them key drug discovery targets for cardiac and neurological indications. Neuronal Nav’s are divided into TTX-sensitive (Nav1.1, Nav1.2, Nav1.3, Nav1.6 and Nav1.7) and TTX-resistant channels (Nav1.8 and Nav1.9), with those found in the CNS underlying various types of epilepsy and those expressed in the periphery implicated in many types of pain behaviour such as inflammatory, neuropathic, chemotherapy and cancer-induced pain, as well as visceral pain conditions such as irritable bowel syndrome (IBS). Key to the role of Navs in pain is their specific distribution and function in peripheral sensory nociceptors of the dorsal root (DRG) and other sensory ganglia, where Nav1.x channel function changes after injury through the effects of inflammatory mediators and signalling pathways, and channels are redistributed from the soma to axons.2 In this way Nav activity increases neuronal excitability and induces spontaneous, persistent, repetitive and ectopic action potential firing. The role of peripheral Navs in pain are supported by the association of SNPs and genetic mutations in Nav1.7 with several pain several phenotypes (CIP, PEPD and IEM)3 and gain-of-function mutations in Nav1.7 and Nav1.8 in human patients suffering from small fibre neuropathy (SFN).
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.
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.