A role for two‐pore potassium (K2P) channels in endometrial epithelial function

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.

Bioelectric Signaling Regulates Size in Zebrafish Fins

“…Studies have proposed that this might occur through regulation of the membrane potential [54]. In apparent contrast to some studies [55]–[58] but in agreement with others [59], [60], we found that hyperpolarization caused by mutations in a K + channel can lead to tissue overgrowth. Although we observed a hyperpolarizing effect of the alf mutation in Xenopus oocytes, we cannot exclude that this, in turn, triggers a depolarization, either at cellular level or in the surrounding tissues during development of the fin.…”

The Evidence of HeLa Cell Apoptosis Induced with Tetraethylammonium Using Proteomics and Various Analytical Methods

“…K ϩ current efflux and anion inflow help maintain cell electroneutrality during the apoptotic volume decrease process (9). Tetraethylammonium (TEA) is a non-selective KChs inhibitor that has been extensively used as a molecular probe to study their structure (10) and characteristics of the regulation pathways (11,12). A four-peptide sequence containing Phe or Tyr residue on the loop surface of KCh proteins is a recognition region for TEA, and it is very conservative (13).…”

Over-expressed human TREK-1 inhibits CHO cell proliferation via inhibiting PKA and p38 MAPK pathways and subsequently inducing G1 arrest

“…Although many studies have suggested that inhibiting TREK-1 expression might promote cell proliferation, some authors have reported different results [14,42] . Specifically, it has been reported that TREK-1 is highly expressed in prostate cancer cells but not in normal prostatic tissues [14] .…”