Mol. Hum. Reprod. Advance Access originally published online on January 5, 2007
Molecular Human Reproduction 2007 13(3):171-179*; doi:10.1093/molehr/gal110
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Mechanical stretch regulates TRPC expression and calcium entry in human myometrial smooth muscle cells
1 Maternal and Fetal Research Unit, Division of Reproduction and Endocrinology, King's College London, St Thomas' Hospital Campus, London 2 Division of Allergy, Asthma and Respiratory Science, King's College, Guy's Hospital Campus, London, UK 3 Department of Pharmacology and Experimental Therapeutics, LSU Health Sciences Center, New Orleans, LA, USA
4 To whom correspondence should be addressed at: Maternal and Fetal Research Unit, Division of Reproduction and Endocrinology, King's College London, St Thomas' Hospital Campus, Lambeth Palace Road, London, SE1 7EH, UK. E-mail: rachel.tribe{at}kcl.ac.uk
Stretch is known to stimulate myometrial hyperplasia and hypertrophy in early pregnancy and uterine contraction at term. We propose that transduction of the stretch signal involves alteration of intracellular calcium signalling, including changes in transient receptor potential canonical (TRPC) isoform expression. The aim of the present study was to investigate the effect of prolonged mechanical (tonic) stretch in vitro on human myometrial smooth muscle cell calcium signalling and TRPC expression. Cells were cultured from myometrial biopsies, obtained from women undergoing elective Caesarean section at term, grown on FlexiplatesTM and subjected to 25% tonic mechanical stretch for 1, 4 and 14 h. Time-matched control cells were not stretched. Mechanical stretch (14 h) increased basal calcium entry and cyclopiazonic acid (CPA)-induced calcium/Mn2+ entry (P < 0.05) in Fura-2 loaded cells. The calcium selectivity of CPA-thapsigarin induced inward currents, measured by patch clamp electrophysiology, was also increased in stretched cells compared with control cells (P < 0.05). Real time PCR and Western blot data demonstrated that TRPC3 and TRPC4 mRNA and TRPC3 protein expression were increased by stretch (P < 0.05), respectively. These data support the hypothesis that uterine stretch modulates uterine growth and contractility in pregnancy via alterations in calcium signalling.
Key words: cell signalling/ion channels/pregnancy/smooth muscle/uterus
* N.B. An error was made in the initial online pagination of Molecular Human Reproduction 13/3. The page span of this article was originally shown as 31–39. The publisher wishes to apologise for this error.
Submitted on August 25, 2006; resubmitted on November 13, 2006; accepted on November 14, 2006.
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