Poster
163

Development and electrophysiological assessment of pain-related ion channel stable cell lines expressing voltage-gated sodium, potassium and TRPs channels

Discussion

Ion channels represent one of the major targets in drug discovery with a direct role in a range of therapeutic areas including pain, neurological disorders and cardiac arrhythmias. SB Drug Discovery has developed a series of constitutive and inducible cell lines expressing voltage- and ligand-gated ion channels which have been shown to be involved in pain-sensation, including sodium (NaV), potassium (KV), transient receptor potential channels (TRP), purinergic (P2X) and anoctamin (ANO) channels. To confirm the presence of functional channels we used a combination of fluorescence (FlexStation) and electrophysiology assays (manual and automated patch-clamp platforms such as Q-Patch and IonWorks). We report consistency of data across the various platforms using specific agonists and antagonists for each characterised channel.
There is considerable evidence that molecules able to specifically act on these channels could have numerous clinical uses, such as in the development of pain relieving drugs and the treatment of epilepsy. For instance, a traditional target for nociception and pain screening is NaV1.7 as mutations in its gene contribute to diseases such as erythromelalgia and paroxysmal extreme pain disorder (PEPD). Another highly investigated target in pain research is the transient receptor potential vanilloid 1 channel (TRPV1) that has been show to be involved in pain transmission. The specific TRPV1 agonist capsaicin has long been known to be a natural compound capable of evoking an intense burning sensation in humans. Furthermore, the anoctamin type 1 channel (ANO-1) has been shown to modify the properties of nociceptive dorsal root ganglion cells, determining their sensitivity to pain.
Here we show high-throughput fluorescent assay data and confirmatory electrophysiological data to validate our stable cell lines. Screening against these ion channels will help identify novel compounds which modulate ion channel behavior and allow for mitigation of pain.

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