Expression and function of potassium channels in the human placental vasculature

Maternal and Fetal Health Research Centre, The University of Manchester, St. Mary’s Hospital, Manchester, United Kingdom Submitted 17 January 2006 ; accepted in final form 24 February 2006 In the placental vasculature, where oxygenation may be an important regulator of vascular reactivity, there is a paucity of data on the expression of potassium (K) channels, which are important mediators of vascular smooth muscle tone. We therefore addressed the expression and function of several K channel subtypes in human placentas. The expression of voltage-gated (K v )2.1, K V 9.3, large-conductance Ca 2+ -activated K channel (BK Ca ), inward-rectified K + channel (K IR )6.1, and two-pore domain inwardly rectifying potassium channel-related acid-sensitive K channels (TASK)1 in chorionic plate arteries, veins, and placental homogenate was assessed by RT-PCR and Western blot analysis. Functional activity of K channels was assessed pharmacologically in small chorionic plate arteries and veins by wire myography using 4-aminopyridine, iberiotoxin, pinacidil, and anandamide. Experiments were performed at 20, 7, and 2% oxygen to assess the effect of oxygenation on the efficacy of K channel modulators. K V 2.1, K V 9.3, BK Ca , K IR 6.1, and TASK1 channels were all demonstrated to be expressed at the message level. K V 2.1, BK Ca , K IR 6.1, and TASK1 were all demonstrated at the protein level. Pharmacological manipulation of voltage-gated and ATP-sensitive channels produced the most marked modifications in vascular tone, in both arteries and veins. We conclude that K channels play an important role in controlling placental vascular function. placenta; human potassium channels; artery; vein Address for reprint requests and other correspondence: M. Wareing, Maternal and Fetal Health Research Centre, The Univ. of Manchester, Division of Human Development, St. Mary’s Hospital, Hathersage Road, Manchester, M13 0JH, UK (e-mail: mark.wareing{at}manchester.ac.uk )