1. Identification of an ionic mechanism for ERα-mediated rapid excitation in neurons.
- Author
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Yu M, Yin N, Feng B, Gao P, Yu K, Liu H, Liu H, Li Y, Ginnard OZ, Conde KM, Wang M, Fang X, Tu L, Bean JC, Liu Q, Deng Y, Yang Y, Han J, Jossy SV, Burt ML, Wong HZ, Yang Y, Arenkiel BR, He Y, Guo S, Gourdy P, Arnal JF, Lenfant F, Wang Z, Wang C, He Y, and Xu Y
- Subjects
- Animals, Female, Humans, Estradiol metabolism, Estradiol pharmacology, Mice, Hypothalamus metabolism, Hypothalamus cytology, Protein Binding, Neurons metabolism, Chloride Channels metabolism, Chloride Channels genetics, Estrogen Receptor alpha metabolism, Estrogen Receptor alpha genetics
- Abstract
The major female ovarian hormone, 17β-estradiol (E
2 ), can alter neuronal excitability within milliseconds to regulate a variety of physiological processes. Estrogen receptor-α (ERα), classically known as a nuclear receptor, exists as a membrane-bound receptor to mediate this rapid action of E2 , but the ionic mechanisms remain unclear. Here, we show that a membrane channel protein, chloride intracellular channel protein-1 (Clic1), can physically interact with ERα with a preference to the membrane-bound ERα. Clic1-mediated currents can be enhanced by E2 and reduced by its depletion. In addition, Clic1 currents are required to mediate the E2 -induced rapid excitations in multiple brain ERα populations. Further, genetic disruption of Clic1 in hypothalamic ERα neurons blunts the regulations of E2 on female body weight balance. In conclusion, we identified the Clic1 chloride channel as a key mediator for E2 -induced rapid neuronal excitation, which may have a broad impact on multiple neurobiological processes regulated by E2 .- Published
- 2024
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