ION Biosciences Thallium Indicators

Labeled thallium indicators are molecules that exhibit an increase in fluorescence upon binding Tl+.

Thallium (Tl⁺)-sensitive fluorescent indicators

Sodium (Na⁺) and potassium (K⁺) are the two most physiologically important monovalent metal cations. Transporters and ion channels for Na⁺ and K⁺ are found in every cell of every known organism and are critical for life. While drugs targeting these channels and transporters are used to treat indications ranging from type II diabetes, to epilepsies, to blood pressure, the therapeutic potential of this incredibly diverse set of proteins remains largely unknown. Therefore, tools to promote the rapid discovery and evaluation of monovalent cation channels and transporters as potential therapeutic targets are badly needed.

While ION’s class-leading Na⁺ and K⁺-sensitive fluorescent indicators are excellent tools for studying cellular Na⁺ and K⁺ dynamics, the relatively small changes in the intracellular concentrations of Na⁺ and K⁺ under normal physiological conditions can make Na⁺ and K⁺ indicators challenging to use, particularly for high-throughput screening (HTS) applications. In many instances, the Tl⁺ flux assay offers an outstanding alternative to K⁺-sensitive and Na+-sensitive fluorescent indicators. 

The Tl⁺ flux assay takes advantage of a Tl⁺-selective fluorescent indicator, Thallos, and the fact that K⁺ and Na⁺ permeable channels and K⁺ and Na⁺ transporters readily accept Tl⁺ as surrogate cation. When Tl⁺ is added to the outside of cells loaded with Thallos, Tl⁺ entering cells through ion channels and transporters permeable to Na⁺ or K⁺ results in a dramatic increase in fluorescence. Although Tl+ flux assay is the most commonly associated with HTS of K⁺ channels, it is equally suitable for HTS of Na⁺ permeable channels and Na+ transporters as well as non-selective, monovalent cation channels.

HeLa cells loaded with Thallos in the presence (+) or the absence (-) of 0.5 mM Tl⁺

Indicator forms and formats

Thallos is a small, synthetic fluorochrome which incorporates a Tl⁺-binding moiety with excellent selectivity for Tl⁺ over most other physiologically relevant metal cations (e.g. Ca²⁺). Under conditions where Tl⁺ is not bound, the fluorescence of the sensor is significantly quenched. When Tl⁺ is bound, the quenching is relieved, and the fluorescence of the sensor dramatically increases.

Thallos is compatible with a wide variety of detectors including fluorescent microscopes, plate readers, flow cytometers. Over the last 20 years, since Dr. David Weaver invented the Tl⁺ flux assay, Tl⁺-sensitive indicators have found numerous uses including high-throughput screening (HTS) of K⁺ channel, Na⁺ channel, other monovalent cation channels, some monovalent cation transporters, and the Gi/o class of G protein-coupled receptors (GPCR) discovery. 

 

(EX 490 nm, EM 515 nm) is the best-in-class Tl⁺-sensitive fluorescent indicator. It boasts outstanding cell loading and excellent compatibility with a wide variety of detectors including fluorescent microscopes, plate readers, and flow cytometers using commonly available filter FITC filters.

(EX 490 nm, EM 515 nm) High-throughput, no wash thallium (Tl⁺) assay. A streamlined solution for large-scale screening of potassium (K⁺), sodium (Na⁺), and non-selective cation channels and their effectors including transporters and GPCRs. 100 plates

(EX 490 nm, EM 515 nm) High-throughput, no wash thallium (Tl⁺) assay. The most flexible solution for measuring the activity of potassium (K⁺), sodium (Na⁺), and non-selective cation channels and their effectors including transporters and GPCRs. 10 plates

Cell permeable, acetoxymethyl group (AM) esters

The native form of Thallos is negatively charged and membrane impermeable. However, masking the negative charge using non-polar, ester-linked moieties (AM esters) allow the molecules to enter cells through passive diffusion. Once inside the cell, ubiquitous intracellular esterase enzymes promote rapid hydrolysis of the AM esters leaving the active, highly polar form of the indicator trapped inside the cell.

Reagents for improving indicator loading, retention and background suppression

Although the AM form of Thallos indicator readily crosses the plasma membrane, there are other factors that can affect how well Thallos loads into cells. Because Thallos-AM is quite hydrophobic, it is common to use the non-ionic surfactant, Pluronic F-127, to improve its solubility in aqueous solution thus improving its loading into cells. Pluronic F-127 at the concentrations employed for loading indicators into cells is generally well tolerated. While Pluronic F-127 isn’t absolutely essential for loading Thallos into cells, it is highly recommended. 

Another factor that can affect cell loading and intracellular localization is the presence of transport proteins capable of transporting many ion-sensitive, fluorescent indicators. In many cell types, the activity of these transporters can result in compartmentalization of the indicators into intracellular compartments as well as extrusion of the indicators outside of the cell. Both of these processes can dramatically reduce the signal-to-background levels and in some cell types (e.g. CHO cells),  make adequate loading of Tl⁺-selective fluorescent indicators nearly impossible. Fortunately, inhibitors of these transport proteins can be an effective means of improving cytoplasmic localization and indicator retention. ION offers a convenient, 100X ION-Pro inhibitor solution that may be used in conjunction with any of our Tl⁺-sensitive fluorescent indicators.

 

Be Brilliant! Explore our line of Thallium Indicators

Our collection of ion indicators targeting Tl flux.

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High-throughput, no wash thallium (Tl⁺) assay. An optimal solution for measuring flux through potassium (K⁺), sodium (Na⁺), and non-selective cation channels and their effectors including transporters and GPCRs. 100 plates

490/515
FITC, GFP
$3,270.00

High-throughput, no wash thallium (Tl⁺) assay. An optimal solution for measuring flux through potassium (K⁺), sodium (Na⁺), and non-selective cation channels and their effectors including transporters and GPCRs. 10 plates

490/515
FITC, GFP
$430.00

Best in class, green fluorescent, thallium (Tl⁺) indicator, membrane permeable. Works with potassium (K⁺), sodium (Na⁺), and monovalent cation channels, and transporters.

490/515
DMSO
FITC, GFP
$495.00
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