Background: KCNQ genes encode for the pore forming α subunits of K_v channels. The KCNQ gene family comprises 5 members (KCNQ1-5), with KCNQ1 expressed predominantly in cardiomyocytes and KCNQ2-5 localised to neurones where they contribute to the resting membrane conductance. The expression products of KCNQ genes exhibit a range of phenotypes due to the formation of heteromultimers within each family and the association with auxiliary (β) subunits encoded by the KCNE gene family, which modulate channel function and pharmacology. There are only a few reports of ion channels encoded by KCNQ in smooth muscle cells and a paucity of information concerning their role in uterine smooth muscle (myometrium). The aim of the present study is to determine the expression profiles of KCNQ and KCNE genes in myometrial tissue from non pregnant mice during the oestrous cycle. Methods: The oestrous cycle of c57/BL6 mice was monitored by daily vaginal smearing and uterine horns dissected at the different stages of the cycle: diestrous (n=5), proestrous (n=5), oestrous (n=5), metestrous (n=5). Total RNA was extracted using Trizol (Invitrogen) and cDNA synthesised with Superscript III (Invitrogen). RT-PCR and qRT-PCR for KCNQ1-5 and KCNE1-5 were performed using tRNA from myometrium and heart/brain (positive controls). qRT-PCR data was quantified using a standard curve and expressed relative to β-Actin. Non-pregnant mouse myometrial strips were used for preliminary in vitro tension measurement (n=3). Results: All of the KCNQ and KCNE isoforms studied were detected in mouse myometrium by RT-PCR but expression levels appeared to vary during the oestrous cycle. qRT-PCR confirmed that KCNE3 was significantly down-regulated in the metestrous group (n= 5, p=0.01), whereas KCNE4 was significantly up-regulated in proestrous group (n = 5, p=0.01), compared to the diestrous group (n =5). Tension studies in vitro indicated that XE991 (1-3 mM, KCNQ channel inhibitor) and retigabine (10μM, KCNQ channel opener) enhanced and attenuated mouse myometrial contractility respectively. Conclusions: We have comprehensively demonstrated the presence of KCNQ and KCNE isoforms in mouse myometrium, which coupled with the preliminary in vitro tension data, suggests a role for the KCNQ channels in the control of uterine contractility. KCNE mRNA expression appears to be regulated in preference to that of KCNQ. The loss of KCNE3, the presence of which promotes KCNQ1 opening, and an increase in KCNE4 mRNA, which inhibits KCNQ1, suggests that regulation of these accessory subunits is an important mechanism for regulating uterine contractility (and hence receptivity) during different stages of the oestrous cycle. Acknowledgements: Supported by Tommy’s the Baby Charity (registered charity no: 1060508)