Detection of KATP channels subunits in human term placental explants and evaluation of their implication in human placental lactogen (hPL) and human chorionic gonadotropin (hCG) release

Abstract

IntroductionATP-sensitive potassium channels (KATP channels) have been identified in a variety of tissues. Nevertheless, the presence and role of such metabolism-sensitive K+ channels still remain to be unraveled in the reproductive system. MethodsThe study evaluates the presence of KATP channel subunits in human term placental explants by immunohistochemistry, proximity ligation assay, Western blot and RT-PCR techniques. The potential involvement of KATP channels in human placental lactogen (hPL) and human chorionic gonadotrophin (hCG) release has been assessed radioimmunologically from human term placental explants incubated in the presence of different KATP channel modulators. ResultsImmunolocalization of the KATP channel subunits documented both the Kir6.2 and SUR2 subunits in the syncytiotrophoblast of human term placenta. Their colocalization was demonstrated by proximity ligation assay and their presence was further confirmed by immunoblotting and RT-PCR. Kir6.1 subunit was immunolocalized in blood vessels media. SUR1 was not expressed at the mRNA level.Incubation of human term placental explants in the presence of increasing concentrations of modulators of KATP channels such as glibenclamide, tolbutamide, pinacidil or diazoxide did not affect the measured hCG and hPL secretory rates. DiscussionOur study reports, for the first time, the presence of the KATP channel subunits Kir6.2 and SUR2 in the human term syncytiotrophoblast. However, under the present experimental conditions, the activation or inhibition of these putative KATP channels by different pharmacological agents did not affect the hPL and hCG secretory rate of human term placental explants. ConclusionThe present findings suggest that the human term syncytiotrophoblast might be endowed with KATP channels. Further studies should clarify their implication in the syncytiotrophoblast ionic homeostasis and hormone regulation.