Park Sung-Hee, Ramachandran Sabarish, Kwon Sang-Hoon, Cha Soon-Do, Seo Eul Won, Bae Insoo, Cho Chiheum, Song Dae-Kyu
Department of Physiology, Keimyung University School of Medicine, Daegu, South Korea.
Gynecol Endocrinol. 2008 May;24(5):250-6. doi: 10.1080/09513590801893315.
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.
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.
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.
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.
本研究的目的是评估人子宫平滑肌瘤平滑肌细胞中ATP敏感性钾（K(ATP)）通道的表达水平，以及该通道在雌激素增强平滑肌瘤生长作用中的参与情况。
采用逆转录-聚合酶链反应（RT-PCR）、实时PCR和蛋白质印迹法对对照子宫肌层和平滑肌瘤细胞中的K(ATP)通道亚基进行鉴定和定量。此外，我们通过全细胞膜片钳记录法测量酶分离的单个子宫平滑肌细胞中的K(ATP)通道活性。通过MTT法测量雌激素诱导的平滑肌瘤细胞增殖。
K(ATP)通道亚基（Kir6.1、Kir6.2、SUR2B）在平滑肌瘤细胞中的表达高于对照细胞。平滑肌瘤细胞中主要通过K(ATP)通道的全细胞电流也更大。浴液中加入雌激素可急性增强通道活性。用K(ATP)通道抑制剂格列本脲预处理可抑制雌激素诱导的平滑肌瘤细胞增殖。
雌激素可能至少部分通过激活K(ATP)通道诱导平滑肌瘤细胞增殖。K(ATP)通道表达增加可能是子宫平滑肌瘤高生长率的一个因果因素。
