These data suggested a role for K+ channels in the regulation of placental blood vessel function. Hampl et al. [25] provided evidence to support these data and further demonstrated, using patch clamp methodologies, that hypoxia significantly reduced KV but not BKCa or KATP-dependent currents in smooth muscle cell isolates from peripheral fetoplacental

vessels. Brereton et al. have added to this literature using whole-cell patch clamping of chorionic plate artery smooth muscle cell isolates [5]; whole-cell currents were inhibited by 4AP, TEA, charybdotoxin, and iberiotoxin supporting the findings of Hampl et al. [25]. In addition, 1-EBIO Caspase inhibitor application significantly increased whole-cell currents, an effect that was abolished/reduced by TRAM-34/apamin, respectively. These data suggested the presence of IKCa and SKCa calcium-activated channels in chorionic plate arterial smooth muscle cells [5]. Protein and mRNA expression data in placental vascular tissues are summarized in Table 1.

As well as their electrophysiological data, Hampl et al. additionally noted expression of several K+ channels including the BKCa and several KV channels (1.5, 2.1, 3.1b) in peripheral fetoplacental vessels [25]. Fyfe et al. have also demonstrated the expression of KV9.3 in both smooth muscle and endothelial cells of placental tissue sections [18]. Brereton et al. similarly noted BKCa channels and furthermore demonstrated IKCa and SKCa3 channel expression CT99021 in vitro in chorionic plate artery smooth muscle isolates

Thymidylate synthase and in intact chorionic plate arteries (although only at the mRNA level for the latter channel). The KIR 6.1 (the pore-forming subunit of the vascular KATP channel) and the “leak” K+ channel TASK1 have also been identified in chorionic plate arteries and veins at the mRNA level [58, 69]. A thorough cataloging of K+ channel expression in placental tissues is lacking. Tissue (endothelium vs. smooth muscle cell) expression data at all levels of the placental vascular tree would be a valuable addition to the literature as this would indicate possible mechanistic roles for K+ channels (e.g., in any EDHF-type response) in the control of vascular function. As noted above, Hampl et al. demonstrated that hypoxia increased pressure in perfused placental cotyledons; this observation was stimulated and/or inhibitable by addition of 4AP [25]. They concluded that KV channels must actively contribute to setting basal placental vascular tone and form a key component in the placental vasculature’s response to altered oxygenation. Bisseling et al. supported this observation that K+ channels are crucial determinants of basal tone [4]; both 4AP and glibenclamide (but neither apamin nor charybdotoxin) increased perfusion pressure suggestive of a role for KV and KATP channels (which are sensitive to oxygenation via their link to intracellular ATP levels/cell metabolism).