17β-estradiol Inhibits Outward Voltage-gated K~+Currents In Human Osteoblast-like MG63Cells

Previous studies have shown that17β-estradiol has a pivotal function by blockingvoltage-gated K+(Kv) channels in several different types of cells such as cardiac myocytesand neurons. Outward Kv currents can also be measured in osteoblasts, although little isknown about the effects of17β-estradiol on these currents. In human osteoblast-like MG63cells, we found that17β-estradiol inhibits peak and end Kv currents, with IC50values of480and325nM, respectively. To elucidate the mechanism of inhibition, the kinetics of Kvcurrents were investigated. The half-maximum activation potential (V1/2) was1.3mV andwas shifted left to-4.4mV after application of500nM17β-estradiol. For steady-stateinactivation, the V1/2was–55.0mV and weakly shifted left to–58.2mV. To identify themolecular basis of outward Kv currents in MG63cells, we performed RT-PCR analyses.The expression of Kv2.1channels appeared to dominate over that of other Kv chan-nels inMG63cells. In COS-7cells with heterologously expressed Kv2.1channels,17β-estradiolalso inhibits macroscopic currents of Kv2.1. Our data indicate that17β-estradiol inhibits Kvcurrents in human osteoblast-like MG63cells and that Kv2.1is a potential molecularcorrelate of outward Kv currents in these cells.