Expresión y actividad de Ca2+-ATPasas en el encéfalo adulto y en desarrollo de distintas especies y en cultivos neuronales

Resumen

Calcium ions play a key role in the activation and regulation of several mechanisms in the nervous system, such as synaptic transmission, neurite development or apoptosis. The fine tuning of intracellular Ca2+ levels is essential for the functioning of these processes and is carried out by Ca2+ pumps SERCA, SPCA, and PMCA. Dysregulation of Ca2+ levels is involved in a neurodegenerative disorder such as Alzheimer disease (AD), being the hippocampus one of the first regions affected by the disease. The goal of this work has been the immunological and functional characterization of Ca2+ pumps in adult pig hippocampus, as well as in developing mouse brain areas. Results show the expression and activities of the pumps in all analyzed areas, being the PMCA the ATPase with the highest activity. The Ca2+-ATPases are localized according to the area and developing stage, being the PMCA expressed in rich synapse regions. Furthermore, the PMCA4 is the only isoform that also is distributed in rafts lipid microdomains. The study has been extended to hippocampal primary neuronal cultures in the absence and presence of A? and calmodulin. The A? affects neuronal survival, cellular morphology and neurite elongation. It has been analyzed their effects on Ca2+-ATPases activity. The A? inhibits specifically the PMCA activity. All A? effects in cultures are prevented by calmodulin. Overall, the results of this work strongly suggest a specific role of Ca2+ pumps in the regulation of this ion in precise functions in brain areas during cellular processes and development.