Expression and function of K(v)7 channels in murine myometrium throughout oestrous cycle.
This study represents an extensive characterisation of the expression and functional impact of KCNQ and KCNE accessory subunits in a murine uterus using a combination of quantitative reverse transcription polymerase chain reaction, Western blot analysis, patch clamp electrophysiology and isometric tension recording. The use of uterine tissue throughout the oestrous cycle provided a physiological model with which to assess hormonal regulation of these genes. Messenger ribonucleic acid for all KCNQ genes were detected throughout the oestrous cycle with the KCNQ1 message predominant. KCNE isoforms were detected at each stage of the cycle. KCNE4 was the most abundant (p < 0.0001), and KCNQ1, KCNQ5 and KCNE1 were up-regulated in metestrous (p < 0.0001). The K(v)7 channel inhibitor XE991 reduced outward K(+) currents and significantly increased spontaneous myometrial contractions (p < 0.05), whereas retigabine (K(v)7 activator) significantly relaxed uterine tissues (p < 0.001). These data are the first to characterise KCNQ and KCNE gene expression in a cell type outside of neurons and the cardiovascular system.
McCallum
Laura A
LA
King's College London, St Thomas' Hospital Campus, UK. laura.mccallum@kcl.ac.uk
Greenwood
Iain A
IA
Tribe
Rachel M
RM
D000818:Animals; D000873:Anthracenes / Q000494:pharmacology; D002219:Carbamates / Q000494:pharmacology; D002839:Chromans / Q000494:pharmacology; D030762:Estrous Cycle / Q000502:physiology*; D005260:Female; D051657:KCNQ1 Potassium Channel / Q000096:biosynthesis / Q000187:drug effects / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D009215:Myometrium / Q000502:physiology*; D010655:Phenylenediamines / Q000494:pharmacology; D026902:Potassium Channel Blockers / Q000494:pharmacology; D024642:Potassium Channels, Voltage-Gated / Q000096:biosynthesis / Q000502:physiology*; D013449:Sulfonamides / Q000494:pharmacology; D014590:Uterine Contraction / Q000187:drug effects
C112297:10,10-bis(4-pyridinylmethyl)-9(10H)-anthracenone; D000873:Anthracenes; D002219:Carbamates; D002839:Chromans; D051657:KCNQ1 Potassium Channel; C092068:Kcne1 protein, mouse; C496910:Kcnq1 protein, mouse; D010655:Phenylenediamines; D026902:Potassium Channel Blockers; D024642:Potassium Channels, Voltage-Gated; D013449:Sulfonamides; C101866:ezogabine; C103474:6-cyano-4-(N-ethylsulfonyl-N-methylamino)-3-hydroxy-2,2-dimethylchromane