Abstract
The human endometrial epithelium is pivotal to menstrual cycle progression, implantation and early pregnancy. Endometrial function is directly regulated by local factors that include pH, oxygen tension and ion concentrations to generate an environment conducive to fertilization. A superfamily of potassium channels characterized by two-pore domains (K2P) and encoded by KCNK genes is implicated in the control of the cell resting membrane potential through the generation of leak currents and modulation by various physicochemical stimuli. The aims of the study were to determine the expression and function of K2P channel subtypes in proliferative and secretory phase endometrium obtained from normo-ovulatory women and in an endometrial cancer cell line. Using immunochemical methods, real-time qRT-PCR proliferation assays and electrophysiology. Our results demonstrate mRNA for several K2P channel subtypes in human endometrium with molecular expression of TREK-1 shown to be higher in proliferative than secretory phase endometrium (P < 0.001). The K2P channel blockers methanandamide, lidocaine, zinc and curcumin had antiproliferative effects (P < 0.01) in an endometrial epithelial cancer cell line indicating a role for TASK and TREK-1 channels in proliferation. Tetraethylammonium- and 4-aminopyridine-insensitive outwards currents were inhibited at all voltages by reducing extracellular pH from 7.4 to 6.6. Higher expression of TREK-1 expression in proliferative phase endometrium may, in part, underlie linked to increased cell division. The effects of pH and a lack of effect of non-specific channel blockers of voltage-gated potassium channels imply a role for K2P channels in the regulation of human endometrial function.
DOI
10.1111/j.1582-4934.2012.01656.x
Publication Date
2013-01-01
Publication Title
Journal of Cellular and Molecular Medicine
Volume
17
Issue
1
Publisher
Wiley
ISSN
1582-4934
Embargo Period
2024-11-19
First Page
134
Last Page
146
Recommended Citation
Patel, S., Jackson, L., Warren, A., & et al. (2013) 'A role for two‐pore potassium (K2P) channels in endometrial epithelial function', Journal of Cellular and Molecular Medicine, 17(1), pp. 134-146. Wiley: Available at: https://doi.org/10.1111/j.1582-4934.2012.01656.x
