As research into ion channels continues to identify novel targets for multiple and diverse diseases, therapeutic successes surrounding the development of channel modulators will boom. Numerous companies are engaged in R&D programs involving ion channels in a number of areas, including asthma, inflammation, arrhythmia and CNS disorders, and drugs targeting ion channels already generate over $6 billion in sales per annum. Despite their remarkable physiological value, ion channels have remained a relatively unexploited therapeutic target, especially in comparison to G-protein coupled receptors or kinases. The slow development of high throughput screening (HTS) tools has been the main factor to limit an explosion in ion channel R&D. The report mentioned above offers an analysis of the ion channel field and includes sections on emerging ion channel targets as well as assays in development to facilitate the screening of molecules that modulate their activity. One channel that is featured and which is receiving growing interest in the scientific community is the voltage-gated K + channel, Kv1.3.

The Kv1.3 channel is one of two potassium channels expressed by human T lymphocytes that are involved in proliferation and cytokine secretion (the other is the calcium-activated K + channel IKCa1). Researchers at the University of California have recently reported that myelin-reactive encephalitogenic rat T cells expressed unusually high numbers of Kv1.3 channels following antigenic stimulation. Furthermore adoptive transfer of these T cells induced multiple sclerosis-like inflammation in rats, an effect which was reduced by Kv1.3 blockade. The search for Kv1.3 blockers or molecules able to prevent channel expression could therefore provide novel anti-inflammatory molecules. Indeed Merck researchers have recently published a series of Kv1.3 channel inhibitors for the potential treatment of autoimmune diseases. The group at the University of California have now developed a fluorescently labeled toxin that when coupled to flow cytometry can assay Kv1.3 expression in chronically activated rat and human T lymphocytes. This assay has a considerably higher throughput potential than other currently available techniques used in the measurement of channel expression such as patch clamp, RT-PCR and Western blot. The assay therefore has multiple uses ranging from cell sorting to the identifications of mechanisms involved in the over-expression of Kv1.3 and therapeutic candidates that can prevent this occurrence. 

Entry date January, 2003

Adapted from Beeton et al, J Biol Chem 2003 Jan 2; [epub ahead of print] - Interested in collaborating with this group? Contact LeadDiscovery or the authors direct.