For more than three decades, our research work has focused on studying the basic mechanisms of cell communication, especially the electrochemical language that forms the basis of this communication. More specifically, our group has directed much of its efforts towards elucidating the basic mechanisms that regulate excitation-secretion coupling phenomena, in which Ca2+ acts as a messenger.

To this end, we have mainly used the chromaffin cell of the adrenal medulla, isolated in primary cultures or in situ in slices. In this cellular model we have studied the subtypes of voltage-activated calcium channels (VACCs) and the different subtypes of neuronal nicotinic receptors expressed by chromaffin cells from different mammalian species, the fine mechanisms that control cellular calcium homeostasis, and the quantal release responses, by exocytosis, of the catecholamines noradrenaline and adrenaline, as well as endocytosis. Together, these experiments led us to formulate the functional triad hypothesis, which includes the leading role of VACCs, the endoplasmic reticulum (ER) and the mitochondria in regulating calcium signals and exo-endocytosis.

Over the last five years, we have tried to apply this basic knowledge to disease models, including arterial hypertension, Alzheimer's disease (AD) and amyotrophic lateral sclerosis (ALS), in which we have found alterations in the kinetics of the fusion pore, which controls the final stages of exocytotic neurotransmitter release. For example, in the chromaffin cells of the APP/PS1 mouse we found an alteration in the kinetics of the fusion pore, which controls the final stages of exocytotic neurotransmitter release. Similarly, results obtained in chromaffin cells from the SOD1G93A mouse model of amyotrophic lateral sclerosis (ALS) indicate an alteration opposite to that found in AD. These data lead to the hypothesis that there is an alteration of the functional triad that controls calcium signals and exo-endocytotic responses in the chromaffin cell.

The scientific impact of these lines of research has 3 dimensions: (a) understanding the alterations in calcium homeostasis and the final stages of exocytosis that could help us better understand the synaptic dysfunctions leading to neurological deficits in AD and ALS; (b) finding new markers for the early diagnosis of these diseases; and (c) inspiring new targets for the development of new drugs with neuroprotective potential in AD and ALS.
Our work is reflected in 104 articles published in internationally circulated peer-reviewed journals (having received close to 3000 citations and with an h-index of 31), 47 articles in nationally circulated journals, and 26 monographs in national and international books.