College of Biomedical Engineering, South-Central University for Nationalities, 708 Minyuan Road, Wuhan 430074, People's Republic of China.
J Membr Biol. 2013 Jan;246(1):39-45. doi: 10.1007/s00232-012-9502-y. Epub 2012 Sep 14.
Previous studies have shown that 17β-estradiol has a pivotal function by blocking voltage-gated K⁺ (Kv) channels in several different types of cells such as cardiac myocytes and neurons. Outward Kv currents can also be measured in osteoblasts, although little is known about the effects of 17β-estradiol on these currents. In human osteoblast-like MG63 cells, we found that 17β-estradiol inhibits peak and end Kv currents, with IC₅₀ values of 480 and 325 nM, respectively. To elucidate the mechanism of inhibition, the kinetics of Kv currents were investigated. The half-maximum activation potential (V(½)) was 1.3 mV and was shifted left to -4.4 mV after application of 500 nM 17β-estradiol. For steady-state inactivation, the V(½) was -55.0 mV and weakly shifted left to -58.2 mV. To identify the molecular basis of outward Kv currents in MG63 cells, we performed RT-PCR analyses. The expression of Kv2.1 channels appeared to dominate over that of other Kv channels in MG63 cells. In COS-7 cells with heterologously expressed Kv2.1 channels, 17β-estradiol also inhibits macroscopic currents of Kv2.1. Our data indicate that 17β-estradiol inhibits Kv currents in human osteoblast-like MG63 cells and that Kv2.1 is a potential molecular correlate of outward Kv currents in these cells.
先前的研究表明，17β-雌二醇通过阻断几种不同类型的细胞中的电压门控钾离子（Kv）通道，发挥关键作用，如心肌细胞和神经元。在外向 Kv 电流也可以在成骨细胞中测量，尽管对 17β-雌二醇对这些电流的影响知之甚少。在人成骨样 MG63 细胞中，我们发现 17β-雌二醇抑制峰和结束 Kv 电流，IC₅₀值分别为 480 和 325 nM。为了阐明抑制机制，研究了 Kv 电流的动力学。Kv 电流的半最大激活电位（V(½)）为 1.3 mV，在应用 500 nM 17β-雌二醇后向左移动至-4.4 mV。对于稳态失活，V(½)为-55.0 mV，向左弱移至-58.2 mV。为了鉴定 MG63 细胞外向 Kv 电流的分子基础，我们进行了 RT-PCR 分析。Kv2.1 通道的表达似乎比 MG63 细胞中的其他 Kv 通道更占主导地位。在表达 Kv2.1 通道的 COS-7 细胞中，17β-雌二醇也抑制 Kv2.1 的宏观电流。我们的数据表明，17β-雌二醇抑制人成骨样 MG63 细胞中的 Kv 电流，并且 Kv2.1 是这些细胞外向 Kv 电流的潜在分子相关物。
