17β-Estradiol Upregulated Expression of α and β Subunits of Larger-Conductance Calcium-Activated K(+) Channels (BK) via Estrogen Receptor β.

Large-conductance Ca(2+)-activated K(+) channels, which were known as BK channels, were widely distributed in brain tissues and played a crucial role in neuroprotection. Previous studies found that estrogen, a steroid hormone, was able to interact with distinct K(+) channels such as Kv (voltage-gated K(+) channels) in various tissues. However, current knowledge about possible effects of estrogen on BK channels is rather poor. In the present study here, the investigation for the interaction of estrogen with BK channels was performed in mouse N2A cells and human SK-N-SH cells. At first, the different expression patterns of α and β subunits of BK channels in these cells were explored by conducting RT-PCR. After exposure to varying dose of 17β-estradiol (E2) for 24 h, the messenger RNA (mRNA) levels of these BK channel subunits in both N2A and SK-N-SH cells were significantly increased in a concentration-dependent way. A prolonged incubation for 48 h also potentiated the effects of E2 on β1 and β4 subunits in N2A cells as well as α and β3 subunits in SK-N-SH cells. The small interfering RNAs (siRNAs) against the ERα (siERα) or ERβ (siERβ) was induced into N2A and SK-N-SH cells by transfection and resulted in a decrease in the level of corresponding ER transcript. Furthermore, treatment with siERβ but not siERα attenuated the action of E2 on BK channel subunits, suggesting that estradiol exerted its action by binding to ERβ. Our data indicated that 17β-estradiol was able to regulate the expression of BK channel subunits via ERβ.