Inflammatory mediators as modulators of decidual calcium channel expression and function. (360G-Wellcome-085528_Z_08_Z)

Proinflammatory pathways have been implicated in the initiation of term and preterm labour. However the specific molecular mechanisms mediating their actions have not been fully elucidated. Our earlier studies have demonstrated the differential expression of decidual potassium and calcium currents with the onset of labour and their modulation by uterotonic agents including oxytocin. We aim to extend our research to test the hypothesis that decidual calcium channels play a key role in integrating cellular signals in preparation for labour and are targets of proinflammatory mediators through which decidual function may be linked to the onset of labour. The unique electrical and immune characteristics of decidual stromal cells as well as their location at the materno-fetal interface suggest that they have key roles in determining uterine function. A combination of molecular techniques and electrophysiology will be utilised to identify and characterise the interaction between voltage-gate d calcium channels and their transcriptional regulation by proinflammatory mediators, in human decidua obtained before and after the onset of labour, These studies will illuminate our understanding of the interplay between complex inflammatory networks and ion channels in the intitiation of spontaneous labour.