Kv1.3 channels are expressed in T-cell lymphocytes and over-expressed in autoimmune diseases. They can be see as a therapeutic taget for T cell mediated autoimmune diseases.
ShK toxin (Stichodactyla helianthus neurotoxin) can be isolated from the venom of the Carribean sea anemone¬ Stoichactis helianthus. Wild-type¬†ShK toxin blocks potently Kv1.3 (KCNA3), Kv1.1 (KCNA1), Kv1.4 (KCNA4) and Kv1.6 (KCNA6) ion chanels with a Kd value of 11 pM, 16 pM, 312 pM and 165 pM, respectively. (Beeton et al., PNAS 103 (46): 17414‚Äď19 (2006))
Recently, Smartox Biotechnology,¬†a biotech¬†company specialized in venom-derived toxins which usually act as ion channel modulators, have developed a fluorescent toxin for ion channel studies.
A fluorescent labeled¬†ShK toxin: TMR ShK
This¬ fluorescent (red) version of the ShK toxin¬†allows to localize the ion channel by confocal microscopy, or to discriminate between cells overexpressing or not Kv1.3 by FACS with higher sensitivity than an anti-Kv1.3 fluorescent antibody.
TMR-ShK blocks Kv1.3 at picomolar concentrations with a Hill coefficient of 1 and exhibited >80-fold specificity for Kv1.3 over Kv1.1 and other K(V) channels.¬†In FACS experiments, it specifically stains Kv1.3-expressing cells with a detection limit of approximately 600 channels per cell (Beeton et al., J Biol Chem. 278 (11): 9928-37 (2003)). It can be used to identify lymphocytes expressing Kv1.3 channels such as effective memory T cells (TEM) in the case of autoimmune diseases (type 1 diabetes, mellitus or rheumatoid arthritis) which overexpress Kv1.3 channels.
TMR ShK toxin¬†can thus¬†be of interest for researchers using conventional immuno-assays.
What about you?
A wide range of synthetic ion channel modulators is now available. What about you? Which ones are you using?