Upregulation of ATP-sensitive potassium channels for estrogen-mediated cell proliferation in human uterine leiomyoma cells

Abstract

Objectives. The objectives of the present study were to evaluate the expression level of ATP-sensitive potassium (K_ATP) channels in smooth muscle cells in human uterine leiomyoma and the involvement of the channel in potentiating effect of estrogen on leiomyoma growth.

Methods. Reverse transcription–polymerase chain reaction (RT-PCR), real-time PCR and Western blot were used for the identification and quantification of K_ATP-channel subunits in the control myometrial and leiomyoma cells. Furthermore, we measured the K_ATP-channel activity in enzymatically isolated single uterine smooth muscle cells by whole-cell patch-clamp recordings. The estrogen-induced cell proliferation in leiomyoma was measured by the MTT assay.

Results. The subunits of K_ATP channels (Kir6.1, Kir6.2, SUR2B) were more highly expressed in leiomyoma cells than in control cells. The whole-cell currents mainly through K_ATP channels were also greater in the leiomyoma cells. Estrogen applied in the bath solution could acutely enhance the channel activity. Estrogen-induced proliferation of the leiomyoma cells was inhibited by pretreatment with glibenclamide, a K_ATP-channel inhibitor.

Conclusion. Estrogen may induce the proliferation of leiomyoma cells, at least in part, by activating the K_ATP channel. Increased expression of the K_ATP channel may be a causal factor for the high growth rate of uterine leiomyoma.

Keywords:

• Uterine leiomyoma
• K_ATP channel
• estrogen
• cell proliferation