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K+ channel inhibition modulates the biochemical and morphological differentiation of human placental cytotrophoblast cells in vitro.
Am J Physiol Regul Integr Comp Physiol. 2008 Oct; 295(4):R1204-13.AJ

Abstract

Maintaining placental syncytiotrophoblast, a specialized multinucleated transport epithelium, is essential for normal human pregnancy. Syncytiotrophoblast continuously renews through differentiation and fusion of cytotrophoblast cells, under paracrine control by syncytiotrophoblast production of human chorionic gonadotropin (hCG). We hypothesized that K(+) channels participate in trophoblast syncytialization and hCG secretion in vitro. Two models of normal-term placenta were used: 1) isolated cytotrophoblast cells and 2) villous tissue in explant culture. Cells and explants were treated with K(+) channel modulators from 18 h, and day 3, onward, respectively. Culture medium was analyzed for hCG, to assess secretion, as well as for lactate dehydrogenase (LDH), to indicate cell/tissue integrity. hCG was also measured in cytotrophoblast cell lysates, indicating cellular production. Syncytialization of cytotrophoblast cells was assessed by immunofluorescent staining of desmosomes and nuclei. Over 18-66 h, mononucleate cells fused to form multinucleated syncytia, accompanied by a 28-fold rise in hCG secretion. 1 mM Ba(2+) stimulated cytotrophoblast cell hCG secretion at 66 h compared with control, whereas 5 mM tetraethylammonium (TEA) inhibited hCG secretion by >90%. 0.1-1 mM 4-aminopyridine (4-AP) reduced cytotrophoblast cell hCG secretion and elevated cellular hCG; without altering cellular integrity or syncytialization. In villous explants, hCG secretion was not altered by 1 mM Ba(2+) but inhibited by 5 mM 4-AP and 5/10 mM TEA, without affecting LDH release. Anandamide, pinacidil, and cromakalim were without effect in either model. In conclusion, 4-AP- and TEA-sensitive K(+) channels (e.g., voltage-gated and Ca(2+)-activated) regulate trophoblast hCG secretion in culture. If these K(+) channels participate in hCG secretion in situ, they may regulate trophoblast turnover in health and disease.

Authors+Show Affiliations

Maternal and Fetal Health Research Group, The Univ. of Manchester, Research Floor, St. Mary's Hospital, Hathersage Road, Manchester, M13 0JH. joanna.williams@postgrad.manchester.ac.ukNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

18703414

Citation

Williams, J L R., et al. "K+ Channel Inhibition Modulates the Biochemical and Morphological Differentiation of Human Placental Cytotrophoblast Cells in Vitro." American Journal of Physiology. Regulatory, Integrative and Comparative Physiology, vol. 295, no. 4, 2008, pp. R1204-13.
Williams JL, Fyfe GK, Sibley CP, et al. K+ channel inhibition modulates the biochemical and morphological differentiation of human placental cytotrophoblast cells in vitro. Am J Physiol Regul Integr Comp Physiol. 2008;295(4):R1204-13.
Williams, J. L., Fyfe, G. K., Sibley, C. P., Baker, P. N., & Greenwood, S. L. (2008). K+ channel inhibition modulates the biochemical and morphological differentiation of human placental cytotrophoblast cells in vitro. American Journal of Physiology. Regulatory, Integrative and Comparative Physiology, 295(4), R1204-13. https://doi.org/10.1152/ajpregu.00193.2008
Williams JL, et al. K+ Channel Inhibition Modulates the Biochemical and Morphological Differentiation of Human Placental Cytotrophoblast Cells in Vitro. Am J Physiol Regul Integr Comp Physiol. 2008;295(4):R1204-13. PubMed PMID: 18703414.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - K+ channel inhibition modulates the biochemical and morphological differentiation of human placental cytotrophoblast cells in vitro. AU - Williams,J L R, AU - Fyfe,G K, AU - Sibley,C P, AU - Baker,P N, AU - Greenwood,S L, Y1 - 2008/08/13/ PY - 2008/8/16/pubmed PY - 2008/12/17/medline PY - 2008/8/16/entrez SP - R1204 EP - 13 JF - American journal of physiology. Regulatory, integrative and comparative physiology JO - Am J Physiol Regul Integr Comp Physiol VL - 295 IS - 4 N2 - Maintaining placental syncytiotrophoblast, a specialized multinucleated transport epithelium, is essential for normal human pregnancy. Syncytiotrophoblast continuously renews through differentiation and fusion of cytotrophoblast cells, under paracrine control by syncytiotrophoblast production of human chorionic gonadotropin (hCG). We hypothesized that K(+) channels participate in trophoblast syncytialization and hCG secretion in vitro. Two models of normal-term placenta were used: 1) isolated cytotrophoblast cells and 2) villous tissue in explant culture. Cells and explants were treated with K(+) channel modulators from 18 h, and day 3, onward, respectively. Culture medium was analyzed for hCG, to assess secretion, as well as for lactate dehydrogenase (LDH), to indicate cell/tissue integrity. hCG was also measured in cytotrophoblast cell lysates, indicating cellular production. Syncytialization of cytotrophoblast cells was assessed by immunofluorescent staining of desmosomes and nuclei. Over 18-66 h, mononucleate cells fused to form multinucleated syncytia, accompanied by a 28-fold rise in hCG secretion. 1 mM Ba(2+) stimulated cytotrophoblast cell hCG secretion at 66 h compared with control, whereas 5 mM tetraethylammonium (TEA) inhibited hCG secretion by >90%. 0.1-1 mM 4-aminopyridine (4-AP) reduced cytotrophoblast cell hCG secretion and elevated cellular hCG; without altering cellular integrity or syncytialization. In villous explants, hCG secretion was not altered by 1 mM Ba(2+) but inhibited by 5 mM 4-AP and 5/10 mM TEA, without affecting LDH release. Anandamide, pinacidil, and cromakalim were without effect in either model. In conclusion, 4-AP- and TEA-sensitive K(+) channels (e.g., voltage-gated and Ca(2+)-activated) regulate trophoblast hCG secretion in culture. If these K(+) channels participate in hCG secretion in situ, they may regulate trophoblast turnover in health and disease. SN - 0363-6119 UR - https://www.unboundmedicine.com/medline/citation/18703414/K+_channel_inhibition_modulates_the_biochemical_and_morphological_differentiation_of_human_placental_cytotrophoblast_cells_in_vitro_ L2 - https://journals.physiology.org/doi/10.1152/ajpregu.00193.2008?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub=pubmed DB - PRIME DP - Unbound Medicine ER -