(1191-D) A cell- and organelle-targetable thallium indicator for fluorescence-based ion channel assays
Tuesday, February 6, 2024
2:00 PM – 3:00 PM EST
Location: Exhibit Halls AB
Abstract: Ion channels are essential transmembrane proteins involved in many physiological processes that are also associated with numerous pathologies when their function is perturbed. Fluorescent ion indicators allow researchers to study ion channel activity by measuring the flux of ions through a channel of interest. More specifically, Thallos, a thallium-selective indicator, has been the gold standard for decades to identify modulators of potassium channels, sodium channels, and monovalent transporters. In this work, we synthesized ION Thallos-HTL, a thallium indicator functionalized with a chloroalkane moiety as a substrate for the self-labeling protein HaloTag. Fluorescence titrations and fluorescence polarization data demonstrate that this new indicator is a substrate for HaloTag, remains sensitive towards thallium ions as the HaloTag conjugate, and exhibits a higher fluorescence response than its parent compound. Live cell experiments showed that specific labeling of cells and intracellular compartments can be achieved. Furthermore, the indicator remains functional as an increase in fluorescence intensity is observed after the addition of thallium - potentially enabling cell-targetable and organellar-specific ion channel assays.