17β-estradiol Downregulated The Expression Of TASK-1Channels In Mouse Neuroblastoma N2A Cells And Promoted Cell Proliferation

TASK channels, a subgroup of two pore domain K+(K2P) channels family, were widelyexpressed in a variety of neural tissues and cells, and exhibited potent functions such as theregulation of membrane potential and cell excitability. The steroid hormone estrogen was ableto protect nerve and interact with K+channels, including voltage-gated K+(Kv) and largeconductance Ca2+-activated (BK) K+channels, in different types of cells like cardiacmyocytes and neurons. However, it is unclear about the effects of estrogen on TASK channelswhich were reported to relate to neuroprotection. In the present study, the expressions of twomembers of acidsensitive TASK channels, TASK-1and TASK-2, were detected in mouseneuroblastoma N2A cells by RT-PCR. Extracellular acidification (pH6.4) weakly butstatistically significantly inhibited the outward background current by22.9%at a holdingpotential of0mV, which inactive voltage-gated K+currents, suggesting that there existed thefunctional TASK channels in the membrane of N2A cells. Although these currents were notaltered by the acute application of100nM17β-estradiol, incubation with10nM17β-estradiolfor48h reduced the mRNA level of TASK-1channels by40.4%without any effect onTASK-2channels. The proliferation rates of N2A cells were also increased by treatment with10nM17β-estradiol for48h. These data implied that N2A cells expressed functional TASKchannels and chronic exposure to17β-estradiol downregulated the expression of TASK-1channels and improved cell proliferation. The further study shows that the expression of themRNA level of TASK-1was significantly knckdowned after transfected by siRNA againstTASK-1for48h, and by the same treatment the growth rate of N2A cells was increased.Conclusions:(1) N2A cells expressed functional TASK channels;(2) Acute applicationof17β-estradiol had no effect on the TASK current;(3) Chronic incubation of17β-estradiolreduced the expression of TASK-1and improved the growth rate of N2A cells;(4) Thegrowth rate of N2A cells was increased when TASK-1was knckdowned by the specificsiRNA.Our study suggests that estrogen probably exerted neuroprotective effect throughdownregulating the expression of TASK-1.