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The endoplasmic reticulum is an abundant, dynamic and energy-sensing organelle. Its abundant membranes, rough and smooth, are distributed in different proportions depending on the cell lineage and requirement. Its function is to carry out protein and lipid synthesis, and it is the main intracellular Ca2+ store. Caloric overload and glycolipotoxicity generated by hypercaloric diets cause alteration of the endoplasmic reticulum, activating the Unfolded Protein Response (UPR) as a reaction to cellular stress related to the endoplasmic reticulum and whose objective is to restore the homeostasis of the organelle by decreasing oxidative stress, protein synthesis and Ca2+ leakage. However, during chronic stress, the UPR induces reactive oxygen species formation, inflammation and apoptosis, exacerbating the state of the endoplasmic reticulum and propagating a deleterious effect on the other organelles. This is why endoplasmic reticulum stress has been considered an inducer of the onset and development of metabolic diseases, including the aggravation of COVID-19. So far, few strategies exist to reestablish endoplasmic reticulum homeostasis, which are targeted to sensors that trigger UPR. Therefore, the identification of new mechanisms and novel therapies related to mitigating the impact of endoplasmic reticulum stress and associated complications is urgently warranted. [ABSTRACT FROM AUTHOR]

This work analyses the role of intracellular calcium pools in serotonin release from nerve terminals. Experiments were carried out in synapses formed in culture between serotonergic Retzius neurones and pressure mechanosensory neurons, isolated from the Central Nervous System of the leech. In this configuration, serotonin is released from clear vesicles at synapses or from extrasynaptic dense core vesicles. Locking ryanodine receptors in a sub-conductance state by incubation with 100 µM ryanodine caused an elongation of the synaptic potential in response to a presynaptic action potential or to trains of them, suggesting that calcium released from the endoplasmic reticulum through these channels reaches the synaptic vesicles and may promote their fusion with the plasma membrane. By contrast, depletion of intracellular calcium pools by incubation with 500 nM thapsigargin gradually decreased paired-pulse synaptic facilitation and abolished extrasynaptic axonal serotonin release in response to trains of impulses. All this occurred without changes in the properties of the postsynaptic membrane, indicating that intracellular calcium release participates in a feedback mechanism that enhances presynaptic and perisynaptic release in serotonergic neurons. [ABSTRACT FROM AUTHOR]