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Store-operated Ca2+ entry in first trimester and term human placenta.
L H Clarson1, V H J Roberts, B Hamark
1Academic Unit of Child Health, University of Manchester, St Mary's Hospital, Hathersage Road, Manchester M13 0JH, UK. l.clarson@rowett.ac.uk
The Journal of Physiology
|May 27, 2003
Summary
Store-operated calcium (Ca2+) entry is present in term human placenta syncytiotrophoblast but not in first trimester placenta. Transient Receptor Potential (TRPC) channels, particularly TRPC3, TRPC4, and TRPC6, are implicated in this calcium entry mechanism.
Area of Science:
- Cellular Physiology
- Human Placental Biology
- Ion Channel Function
Background:
- Store-operated Ca2+ entry is a key mechanism for regulating intracellular calcium in non-excitable cells.
- The syncytiotrophoblast plays a critical role in nutrient and gas exchange between mother and fetus.
- Transient Receptor Potential (TRPC) channels are hypothesized to mediate store-operated Ca2+ entry.
Purpose of the Study:
- To investigate the presence and characteristics of store-operated Ca2+ entry in human placental syncytiotrophoblast.
- To examine the expression of TRPC channel homologues at mRNA and protein levels in first trimester and term placentas.
- To determine the role of TRPC channels in placental Ca2+ homeostasis.
Main Methods:
- Measurement of intracellular calcium ([Ca2+]i) using microfluorimetry with fura-2 in placental villous fragments.
- Stimulation of store-operated Ca2+ entry using thapsigargin in a calcium-free buffer followed by calcium re-addition.
- Analysis of TRPC gene and protein expression via RT-PCR, Western blotting, and immunocytochemistry.
Main Results:
- Store-operated Ca2+ entry was successfully induced in term placental syncytiotrophoblast, inhibited by GdCl3, NiCl2, CoCl2, and SKF96365, but not nifedipine.
- No significant store-operated Ca2+ entry was observed in first trimester placental syncytiotrophoblast.
- TRPC1, TRPC3, TRPC4, TRPC5, and TRPC6 mRNA were detected in both placental stages. TRPC3 and TRPC6 proteins were found in term placenta only. TRPC3 and TRPC4 localized to cytotrophoblast (first trimester) and syncytiotrophoblast (term), while TRPC6 was present in syncytiotrophoblast of both, with higher intensity in term placenta.
Conclusions:
- Store-operated Ca2+ entry is likely a significant pathway for calcium influx into the syncytiotrophoblast of term human placenta.
- TRPC channels, specifically TRPC3, TRPC4, and TRPC6, are proposed to mediate this store-operated calcium entry in the human placenta.
- The developmental changes in store-operated Ca2+ entry and TRPC expression suggest a role in placental maturation and function.