title: L-Type Calcium Channels Modulation by Estradiol.
abstract: Voltage-gated calcium channels are key regulators of brain function, and their dysfunction has been associated with multiple conditions and neurodegenerative diseases because they couple membrane depolarization to the influx of calcium-and other processes such as gene expression-in excitable cells. L-type calcium channels, one of the three major classes and probably the best characterized of the voltage-gated calcium channels, act as an essential calcium binding proteins with a significant biological relevance. It is well known that estradiol can activate rapidly brain signaling pathways and modulatory/regulatory proteins through non-genomic (or non-transcriptional) mechanisms, which lead to an increase of intracellular calcium that activate multiple kinases and signaling cascades, in the same way as L-type calcium channels responses. In this context, estrogens-L-type calcium channels signaling raises intracellular calcium levels and activates the same signaling cascades in the brain probably through estrogen receptor-independent modulatory mechanisms. In this review, we discuss the available literature on this area, which seems to suggest that estradiol exerts dual effects/modulation on these channels in a concentration-dependent manner (as a potentiator of these channels in pM concentrations and as an inhibitor in nM concentrations). Indeed, estradiol may orchestrate multiple neurotrophic responses, which open a new avenue for the development of novel estrogen-based therapies to alleviate different neuropathologies. We also highlight that it is essential to determine through computational and/or experimental approaches the interaction between estradiol and L-type calcium channels to assist these developments, which is an interesting area of research that deserves a closer look in future biomedical research.
authors.affiliation: Departamento de Nutrición y Bioquímica, Facultad de Ciencias, Pontificia Universidad Javeriana, Bogotá D.C., Colombia.
authors.forename: Nelson E
authors.initials: NE
authors.lastname: Vega-Vela
authors.affiliation: Departamento de Nutrición y Bioquímica, Facultad de Ciencias, Pontificia Universidad Javeriana, Bogotá D.C., Colombia.
authors.forename: Daniel
authors.initials: D
authors.lastname: Osorio
authors.affiliation: Departamento de Nutrición y Bioquímica, Facultad de Ciencias, Pontificia Universidad Javeriana, Bogotá D.C., Colombia.
authors.forename: Marco
authors.initials: M
authors.lastname: Avila-Rodriguez
authors.affiliation: Departamento de Nutrición y Bioquímica, Facultad de Ciencias, Pontificia Universidad Javeriana, Bogotá D.C., Colombia.
authors.forename: Janneth
authors.initials: J
authors.lastname: Gonzalez
authors.affiliation: Instituto Cajal, CSIC, Madrid, Spain.
authors.forename: Luis Miguel
authors.initials: LM
authors.lastname: García-Segura
authors.affiliation: Universidad San Sebastián, Lientur 1457, 4030000, Concepción, Chile.
authors.forename: Valentina
authors.initials: V
authors.lastname: Echeverria
authors.affiliation: Departamento de Nutrición y Bioquímica, Facultad de Ciencias, Pontificia Universidad Javeriana, Bogotá D.C., Colombia. gsampaio@javeriana.edu.co.|Instituto de Ciencias Biomédicas, Universidad Autónoma de Chile, Santiago, Chile. gsampaio@javeriana.edu.co.
authors.forename: George E
authors.initials: GE
authors.lastname: Barreto
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism*; D020746:Calcium Channels, L-Type / Q000187:drug effects* / Q000378:metabolism; D004958:Estradiol / Q000378:metabolism / Q000494:pharmacology*; D004967:Estrogens / Q000378:metabolism; D006801:Humans; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D020746:Calcium Channels, L-Type; D004967:Estrogens; D004958:Estradiol; D002118:Calcium
keywords: Calcium signaling; DHP binding site; Estradiol; Estrogen non-genomic actions; Estrogen receptor-independent mechanisms; Voltage-gated calcium channels