Abstract
ATP induced ion currents observed in rat myometrial cells are thought to enhance uterine contractility. Though the properties of the currents through myometrial ATP channels were similar to those of P2X channels, the subtype of the channel has not been determined in the uterus. The purpose of this study was to determine which of P2X subtype is mainly expressed in myometrium. We have reported mRNA of P2X4 was detected as a dominant subtype in rat myometrium by quantitative PCR method. The sequence of mRNA of P2X4 was determined and the homology between myometrium and brain was higher than 99%. The cloned mRNA of P2X4 was transfected into the COS-7 cell line that has no ATP current. The whole cell patch clamp method was applied to the COS-7 cells. The expressed P2X4 channel currents were induced by external ATP application in the range between 0.01 and 0.5 mM. This channel was permeable to various monovalent ions (K+ = Cs+ > Na+ > Li+). The current was also activated by ADP, GTP, UTP, 2-methylthio ATP and αβ-methylene ATP, and was blocked by both suramin and PPADS (blockers of P2 and P2X channel). These results indicate that the expressed P2X4 channels resemble to ATP channels in native myometrial cells. However, desensitization to ATP was much faster (<60s) in expressed P2X4 channels, compared with myometrial ATP channels. The expression of P2X channels has been detected in pregnant rat myometrium. P2X4 may be the main functioning channel of myometrial ATP channel, leading to enhancement of uterine contractility. [Jpn J Physiol 55 Suppl:S133 (2005)]