Neurophysiological functions and pharmacological tools of acidic and non-acidic Ca²⁺ stores

Ca²⁺ signalling is of prime importance in controlling numerous cell functions in the brain. Endolysosomes are acidic organelles currently emerging as important Ca²⁺ stores in astrocytes, microglia, endothelial cells, and neurons. In neurons, these acidic Ca²⁺ stores are found in axons, soma, dendrites, and axon endings and could provide local sources of Ca²⁺ to control synaptic transmission, neuronal plasticity, and autophagy to name a few. This review will address how acidic Ca²⁺ stores are recruited in response to cell stimulation. We will focus on the role of the endolysosomal two-pore channels (TPCs) and their physiological agonist nicotinic acid adenine dinucleotide phosphate (NAADP) and how they interact with cyclic ADP-ribose and ryanodine receptors from the endoplasmic reticulum. Finally, this review will describe new pharmacological tools and animal mutant models now available to explore acidic Ca²⁺ stores as key elements in brain function and dysfunction.