Spatial and temporal aspects of neuronal calcium and sodium signals measured with low-affinity fluorescent indicators

Low-affinity fluorescent indicators for Ca²⁺ or Na⁺ allow measuring the dynamics of intracellular concentration of these ions with little perturbation from physiological conditions because they are weak buffers. When using synthetic indicators, which are small molecules with fast kinetics, it is also possible to extract spatial and temporal information on the sources of ion transients, their localization, and their disposition. This review examines these important aspects from the biophysical point of view, and how they have been recently exploited in neurophysiological studies. We first analyze the environment where Ca²⁺ and Na⁺ indicators are inserted, highlighting the interpretation of the two different signals. Then, we address the information that can be obtained by analyzing the rising phase and the falling phase of the Ca²⁺ and Na⁺ transients evoked by different stimuli, focusing on the kinetics of ionic currents and on the spatial interpretation of these measurements, especially on events in axons and dendritic spines. Finally, we suggest how Ca²⁺ or Na⁺ imaging using low-affinity synthetic fluorescent indicators can be exploited in future fundamental or applied research.