L-Type Calcium Channels Modulation by Estradiol

被引:0
|
作者
Nelson E. Vega-Vela
Daniel Osorio
Marco Avila-Rodriguez
Janneth Gonzalez
Luis Miguel García-Segura
Valentina Echeverria
George E. Barreto
机构
[1] Pontificia Universidad Javeriana,Departamento de Nutrición y Bioquímica, Facultad de Ciencias
[2] Instituto Cajal,Instituto de Ciencias Biomédicas
[3] CSIC,undefined
[4] Universidad San Sebastián,undefined
[5] Universidad Autónoma de Chile,undefined
来源
Molecular Neurobiology | 2017年 / 54卷
关键词
Voltage-gated calcium channels; Estradiol; Calcium signaling; Estrogen receptor-independent mechanisms; Estrogen non-genomic actions; DHP binding site;
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学科分类号
摘要
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.
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页码:4996 / 5007
页数:11
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