Diversity of potassium channels in human umbilical artery smooth muscle cells: a review of their roles in human umbilical artery contraction

Abstract

Through their control of cell membrane potential, potassium (K(+)) channels are among the best known regulators of vascular tone. This article discusses the expression and function of K(+) channels in human umbilical artery smooth muscle cells (HUASMCs). We review the bibliographic reports and also present single-channel data recorded in freshly isolated cells. Electrophysiological properties of big conductance, voltage- and Ca(2+)-sensitive K(+) channel and voltage-dependent K(+) channels are clearly established in this vessel, where they are involved in contractile state regulation. Their role in the maintenance of membrane potential is an important control mechanism in the determination of the vessel diameter. Additionally, small conductance Ca(2+)-sensitive K(+) channels, 2-pore domains K(+) channels and inward rectifier K(+) channels also appear to be present in HUASMCs, while intermediate conductance Ca(2+)-sensitive K(+) channels and ATP-sensitive K(+) channels could not be identified. In both cases, additional investigation is necessary to reach conclusive evidence of their expression and/or functional role in HUASMCs. Finally, we discuss the role of K(+) channels in pregnancy-related pathologies like gestational diabetes and preeclampsia.

Keywords: K+ channels; human umbilical artery; patch-clamp.

Figure 1.

Summary of the link between K⁺ channel activity, membrane potential, and smooth muscle contractile state which, in turn, determines a blood vessel diameter.

Figure 2.

Diversity of K⁺ channels in dispersed human umbilical artery (HUA) smooth muscle cells. A, Typical cell-attached single-channel recording in the stationary state (recordings of 30-60 seconds) using symmetrical K⁺ concentrations (assuming an intracellular concentration K⁺ of 140 mmol/L). The arrows indicate the ionic channel conductance values obtained from the slope of the respective current–voltage (IV) curves. B, Distribution of all single-channel conductances observed in HUA smooth muscle cells constructed from records similar to those shown in (A). The resulting histogram was well fitted by a 6-component Gaussian curve (indicated by the solid line; the dotted lines define each of these 6 groups). C, Box diagrams showing the properties of the 6 groups of conductances obtained in (B). For each of the groups are shown the mean conductance value (solid dot inside the box), the median (line inside the box), and the range of conductance values between the 25 and 75 percentiles (box) and between the 5 and 95 percentiles (capped lines). The bars show the relative frequency of appearance of the components of each group. D, Typical cell-attached single-channel recordings obtained as described in (A), showing BK_Ca channel activity and probable subconductance levels (indicated by arrows) for this channel. Bath solution (in mmol/L): 140 potassium chloride (KCl); 0.5 magnesium chloride (MgCl₂); 10 HEPES; 6 glucose; 1 ethylene glycol tetraacetic acid, pH adjusted to 7.4 with potassium hydroxide (KOH). Pipette solution (in mmol/L): 140 KCl; 0.5 MgCl₂; 10 HEPES; 6 glucose; 1 calcium chloride; pH adjusted to 7.4 with KOH.

Figure 3.

4-AP sensitivity of ion channel conductances in human umbilical artery (HUA) smooth muscle cells. Frequency of appearance of the different single-channel conductances recorded in the inside-out configuration in control conditions (n = 65 cells) and with 5 mmol/L 4-AP (n = 100 cells) added to the pipette solution. The symbol * indicates statistically significant difference from control (chi-square test). Bath solution (in mmol/L): 140 potassium chloride (KCl); 0.5 magnesium chloride (MgCl₂); 10 HEPES; 6 glucose; 1 ethylene glycol tetraacetic acid, pH adjusted to 7.4 with potassium hydroxide (KOH). Pipette solution (in mmol/L): 140 KCl; 0.5 MgCl₂; 10 HEPES; 6 glucose; 1 calcium chloride; pH adjusted to 7.4 with KOH.

Figure 4.

Summary of current knowledge regarding K⁺ channel expression and function in human umbilical artery smooth muscle cells. Channels are depicted in different colors depending on the weight of the evidence pointing to their presence and function; black means there is fairly conclusive evidence obtained from different types of experimental techniques, while white (with a question mark) denotes that there is suggestive evidence present (only one type of experimental technique used) but definitive confirmation is needed. In the case of SK_Ca, a possible location in the endothelial cells is also suggested. The numbers 1 through 3 denote possible functions for these channels in these cells. NO,nitric oxide; K_V, voltage-dependent K⁺ channels (different subfamilies); BK_Ca, big conductance, voltage- and Ca²⁺-sensitive K⁺ channel; SK_Ca, small conductance Ca²⁺-sensitive K⁺ channels; K_2P, 2-pore domains K⁺ channels; K_IR, inward rectifier K⁺ channels. Intermediate conductance Ca²⁺-sensitive K⁺ channels (IK_Ca), and ATP-sensitive K⁺ channels (K_ATP) are not include because the evidence about their presence in HUA is either weak (K_ATP) or altogether not present in the literature (IK_Ca).