Abstract
BackgroundPotassium channels play critical roles in the regulation of cell membrane potential, which is central to the excitability of myometrium. The ATP-sensitive potassium (KATP) channel is one of the most abundant potassium channels in myometrium. The objectives of this study were to investigate the protein expression of KATP channel in human myometrium and determine the levels of KATP channel in lower and upper segmental myometrium before and after onset of labour.MethodsBoth lower segmental (LS) and upper segmental (US) myometrial biopsies were collected at cesarean section from pregnant women not-in-labour (TNL) or in-labour (TL) at term. Protein expression level and cellular localization of four KATP channel subunits in US and LS myometrium were determined by Western blot analysis and immunohistochemistry, respectively. The contractile activity of myometrial strip was measured under isometric conditions.ResultsFour KATP channel subunits, namely Kir6.1, Kir6.2, SUR1 and SUR2B were identified in pregnant myometrium. While found in vascular myocytes, these subunits appear to be preferentially expressed in myometrial myocytes. Diazoxide, a KATP channel opener, inhibited the spontaneous contractility of pregnant myometrium, suggesting that the KATP channels are functional in human pregnant myometrium. Diazoxide was less potent in TL strips than that in TNL strips. Interestingly, expression of SUR1 was greater in TL than TNL tissues, although no differences were found for SUR2B in these two tissues. For both lower and upper segmental myometrium, Kir6.1 and Kir6.2 were less in TL compared with TNL tissues.ConclusionsFunctional KATP channels are expressed in human pregnant myometrium. Down-regulation of Kir6.1 and Kir6.2 expression in myometrium may contribute to the enhanced uterine contractility associated with the onset of labour.
Highlights
Potassium channels play critical roles in the regulation of cell membrane potential, which is central to the excitability of myometrium
Expression and localization of KATP channel subunits in pregnant human myometrium Immunohistochemistry revealed that positive immunoreactivity for Kir6.1, Kir6.2, SUR1 and SUR2B subunit was identified in human pregnant myometrium
The effect of KATP channel opener on spontaneous contractility of myometrium strip To confirm the KATP channel activity in pregnant myometrium, we examined the effect of diazoxide, an opener of KATP channels, on spontaneous contractility of lower segmental (LS) strips that were obtained from pregnant women who were undergoing labour or not undergoing labour at term
Summary
Potassium channels play critical roles in the regulation of cell membrane potential, which is central to the excitability of myometrium. Potassium channels play critical roles in the regulation of cell membrane potential, which is central to the excitability and contractility of myometrium [4,5]. The opening of these channels results in K+ efflux, causing the membrane potential to closer to K+ equilibrium potential, and thereby reducing excitability and contractility of the smooth muscle cells. The changes in the expression or activity of K+ channels can translate into a change in excitability and contractility of myometrium
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