Intracellular magnesium detection: imaging a brighter future

Abstract

A wide variety of biochemical reactions and physiological functions are known to require magnesium; nonetheless, its regulatory mechanisms (both at the cellular and systemic level) are still poorly characterised. Derangement of magnesium homeostasis is associated with several relevant human pathologies, e.g. diabetes, neuromuscular disorders, hypertension and other cardiovascular diseases. The study of the regulation of magnesium has gained particular interest in the last decades thanks to the molecular characterisation of specific magnesium transporters and the exploitation of molecular biology techniques to clarify their cellular and physiological function(s). In contrast, experimental tools to trace cellular magnesium and to define its homeostasis in living cells have not witnessed a corresponding progress. It was not until recently that efforts were paid to design more appropriate fluorescent indicators that could translate the advances of live imaging techniques into the field of magnesium research. Herein we critically summarise the state of the art in intracellular magnesium detection by fluorescent probes and focus on the need for improving methods and techniques in this area. We highlight the advantages of last-generation fluorescent indicators and discuss a number of challenges and opportunities that the development of novel and better sensors for magnesium still faces.

Solvent Effect on the Fluorescence Response of Hydroxycoumarin Bearing a Dipicolylamine Binding Site to Metal Ions

“…1 H NMR signals appearing of around 7.0 -8.5 ppm are attributed to the resonance corresponding to the DPA protons of dpa-HC. In contrast to the addition of Mg 2+ , the addition of 1 equiv.…”

“…Moreover, the emergence of metal ion imaging to examine changes in the intracellular distribution and the mobilization upon physiological or pathological stimuli is expected within the decade. 1 In recent years, new fluorescence-based applications have been developed, and some probes have a dipicolylamine (DPA) unit as the ion-recognition site. Dipicolylamine has a tridentate ligand with three nitrogen donors to afford good selectivity for Zn 2+ and Cd 2+ , and leaves the coordination sites free for anion binding.…”

“…1,2 Fluorescent probes with high sensitivity and selectivity have become a powerful non-destructive tool for real-time monitoring. 3,4 Fluorescent probes can sensitively detect toxic metal ions in the environment.…”

Magnesium and Hypertension

“…Research involving new imaging techniques to measure intracellular magnesium, such as P-nuclear magnetic resonance (NMR) and magnesium-speci fi c ion-selective electrodes (ISE), which measure intracellular and extracellular free concentrations of magnesium, and fl uorescent probes will further enhance our understanding of the role of magnesium in hypertension [ 17,49 ] . Intracellular magnesium is a more accurate re fl ection of total body magnesium stores.…”

Combined X-ray Microfluorescence and Atomic Force Microscopy Studies of Mg Distribution in Whole Cells

“…Despite recent efforts in applying new live imaging techniques to the field of Mg research [3], an accurate characterization of Mg distribution in the cellular environment is still lacking. Here we used scanning fluorescence x-ray microscopy (SFXM), a highly sensitive method for mapping elements in cells [4].…”