title: 17β-estradiol downregulated the expression of TASK-1 channels in mouse neuroblastoma N2A cells.
abstract: TASK channels, an acid-sensitive subgroup of two pore domain K⁺ (K2P) channels family, were widely expressed in a variety of neural tissues, and exhibited potent functions such as the regulation of membrane potential. The steroid hormone estrogen was able to interact with K⁺ channels, including voltage-gated K⁺ (Kv) and large conductance Ca²⁺-activated (BK) K⁺ channels, in different types of cells like cardiac myocytes and neurons. However, it is unclear about the effects of estrogen on TASK channels. In the present study, the expressions of two members of acid-sensitive TASK channels, TASK-1 and TASK-2, were detected in mouse neuroblastoma N2A cells by RT-PCR. Extracellular acidification (pH 6.4) weakly but statistically significantly inhibited the outward background current by 22.9 % at a holding potential of 0 mV, which inactive voltage-gated K⁺ currents, suggesting that there existed the functional TASK channels in the membrane of N2A cells. Although these currents were not altered by the acute application of 100 nM 17β-estradiol, incubation with 10 nM 17β-estradiol for 48 h reduced the mRNA level of TASK-1 channels by 40.4 % without any effect on TASK-2 channels. The proliferation rates of N2A cells were also increased by treatment with 10 nM 17β-estradiol for 48 h. These data implied that N2A cells expressed functional TASK channels and chronic exposure to 17β-estradiol downregulated the expression of TASK-1 channels and improved cell proliferation. The effect of 17β-estradiol on TASK-1 channels might be an alternative mechanism for the neuroprotective action of 17β-estradiol.
authors.affiliation: Department of Biomedical Engineering, South-Central University for Nationalities, 182 Minyuan Road, Wuhan, 430074, China.
authors.forename: Xuran
authors.initials: X
authors.lastname: Hao
authors.forename: Xiaoqing
authors.initials: X
authors.lastname: Li
authors.forename: Xiantao
authors.initials: X
authors.lastname: Li
mesh_terms: D000818:Animals; D001921:Brain / Q000378:metabolism; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D015536:Down-Regulation / Q000187:drug effects; D004958:Estradiol / Q000494:pharmacology*; D004967:Estrogens / Q000494:pharmacology; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D051379:Mice; D009419:Nerve Tissue Proteins / Q000235:genetics* / Q000378:metabolism*; D009447:Neuroblastoma / Q000235:genetics* / Q000378:metabolism*; D024683:Potassium Channels, Tandem Pore Domain / Q000235:genetics* / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics
chemical_list: D004967:Estrogens; C498739:Kcnk5 protein, mouse; D009419:Nerve Tissue Proteins; D024683:Potassium Channels, Tandem Pore Domain; D012333:RNA, Messenger; C420132:potassium channel subfamily K member 3; D004958:Estradiol