A role for two-pore potassium (K2P) channels in endometrial epithelial function
Article first published online: 11 JAN 2013
© 2012 The Authors Journal of Cellular and Molecular Medicine Published by Foundation for Cellular and Molecular Medicine/Blackwell Publishing Ltd
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Journal of Cellular and Molecular Medicine
Volume 17, Issue 1, pages 134–146, January 2013
How to Cite
Patel, S. K., Jackson, L., Warren, A. Y., Arya, P., Shaw, R. W. and Khan, R. N. (2013), A role for two-pore potassium (K2P) channels in endometrial epithelial function. Journal of Cellular and Molecular Medicine, 17: 134–146. doi: 10.1111/j.1582-4934.2012.01656.x
- Issue published online: 29 JAN 2013
- Article first published online: 11 JAN 2013
- Manuscript Accepted: 15 OCT 2012
- Manuscript Received: 12 JUL 2012
- menstrual cycle
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.