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Physiological Induction of Transient Receptor Potential Canonical Proteins, Calcium Entry Channels, in Human Myometrium: Influence of Pregnancy, Labor, and Interleukin-1ß

Parturition Research Group (A.D., L.P., R.M.T.), Maternal and Fetal Research Unit, Department of Women’s Health, Guy’s, King’s and St. Thomas’ School of Medicine, St. Thomas’ Hospital Campus, London, SE1 7EH, United Kingdom; and Biochemical Research Institute (D.M.S.), The University of Warwick, Coventry, CV4 7AL, United Kingdom

Address all correspondence and requests for reprints to: Dr. Rachel M. Tribe, Parturition Research Group, Maternal and Fetal Research Unit, Department of Women’s Health, 10th Floor, North Wing, Guy’s, King’s and St. Thomas’ School of Medicine, King’s College London, St. Thomas’ Hospital Campus, Lambeth Palace Road, London, SE1 7EH, United Kingdom. E-mail: rachel.tribe{at}kcl.ac.uk.

This study investigated gestational regulation of transient receptor potential canonical (TrpC) proteins, putative calcium entry channels in human myometrium, and the potential modulation of TrpC expression by IL–1ß, a cytokine implicated in labor. Total RNA and proteins were isolated from myometrial biopsies obtained from NP women, pregnant women at term not in labor (TNL), or term active labor (TAL) and from primary cultured human myometrial smooth muscle cells incubated with IL–1ß or IL–1ß with or without nimesulide. Semiquantitative RT-PCR demonstrated significant up-regulation of TrpC1 in TAL and TNL (P 0.01) and TrpC6 (P 0.01) and TrpC7 (P 0.05) in TAL samples. TrpC3 and TrpC4 mRNA expression was unaffected. Western blot demonstrated significant up-regulation of TrpC1 in TAL and TNL (P 0.05) and TrpC3 (P 0.01), TrpC4 (P 0.05), and TrpC6 (P 0.01) in TAL samples. IL–1ß did not alter TrpC1, 3, 4, 6, or 7 mRNA expression; but IL–1ß exclusively up-regulated TrpC3 protein expression (P 0.05). TrpC3 up-regulation was unaffected by cyclooxygenase blockade. These data demonstrate physiological regulation of TrpC mRNA and protein and suggest an important role for TrpC proteins in human myometrium during labor.

This work was funded by the Wellcome Trust (Grant no. 061138) and Tommys’, the baby charity (Reg. Charity no. 1060508).

Abbreviations: COX, Cyclooxygenase; FCS, fetal calf serum; GAPDH, glyceraldehyde-3-phosphate dehydrogenase; HMSM, human myometrial smooth muscle; M_r, relative molecular mass; NP, nonpregnant; N.S., not significant; SERCA, SR calcium ATPases; SOCE, store-operated calcium entry; SR, sarcoplasmic reticulum; TAL, term active labor; TNL, term not in labor; TrpC, transient receptor potential canonical.

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