The human decidua has a prominent integrative role in uterine physiology, but the molecular mechanisms underlying decidual cell function are poorly understood. Potassium-selective (K⁺) ion channels are ubiquitous in excitable and non-excitable cells, illustrating their importance in coupling chemical and electrical signalling. In this study, we sought to characterize the K⁺ currents in human decidual cells taken either after spontaneous vaginal delivery (SVD, labour) or elective Caesarean section (CS, non-labour) to test the hypothesis that differential activation of K⁺ channels may modulate the cellular excitability of this tissue during gestation.

Decidual cells were isolated from term placentae after SVD or at CS following informed written patient consent and local ethical committee approval. The choriodecidua was stripped from the placenta, enzymatically dispersed with collagenase then centrifuged in Ficoll and Percoll gradients. Whole-cell voltage-clamp recordings were made from freshly dispersed decidual cells held at a variety of holding potentials (V_h -100 to -40 mV) and depolarized to +60 mV in 10 mV increments of 400 ms duration. The internal electrode solution consisted of (mM): 140 KCl, 1 MgCl₂, 0.9 CaCl₂, 1 EGTA and 10 Hepes, pH 7.2; free intracellular Ca²⁺ of 793 nM) and the bath solution (mM) of: 135 NaCl, 5 KCl, 1 CaCl₂, 1 MgCl₂ and 10 Hepes, pH 7.2). Current amplitudes were normalized to cell capacitance and plotted as a function of test potentials. Both resting membrane potentials and action potentials (AP) were recorded under current-clamp. The effects of known K⁺ channel blockers were also compared in cells from SVD or CS. All pulse protocols and data acquisition was performed with an EPC-9 amplifier controlled by Pulse/Pulsefit (V8.31; HEKA, Germany). Results, expressed as means ± S.D. of n observations, were compared using Student’s unpaired t test.

Decidual cells had respective resting membrane potentials of -46.89 ± 9.85 (n = 14) and -44.18 ± 12.65 mV (n = 12) in the SVD and CS groups. Current injection elicited AP in both CS (n = 6) and SVD (n = 6) cells, but no statistical difference in AP parameters was observed between these two groups. Membrane capacitance, as an indicator of cell membrane area, was not significantly different between SVD and CS cells, averaging 103.75 ± 17.27 pF (n = 12) and 104.61 ± 33.64 pF (n = 15), respectively. Step depolarizations of human decidual cells from V_h values of -40, -60, -80 or -100 mV to +60 mV led to the activation of slowly activating outward currents. Pharmacological dissection of the currents with 100 nM iberiotoxin, a BK_Ca channel blocker, reduced mean outward current of decidual cells obtained from SVD by 31.85 % (n = 12) compared with 20.22 % in CS (n = 15; P = 0.032). Paxilline, also a BK_Ca channel blocker (1 µM), had little effect on both groups whilst E4031, an inhibitor of the rapidly activating delayed rectifier, inhibited outward currents by 28.52 % (n = 14) compared with 7.36 % (n = 14) in cells from SVD and CS, respectively. Cells from both SVD and CS expressed an inwardly rectifying potassium conductance activated by depolarization from a V_h of -100 mV (n = 27).

The much greater effect of iberiotoxin and E4031 on outward currents in cells from SVD compared with CS indicates a temporal shift in K⁺ channel function in decidual cells with the onset of labour. This may be related to the return of the uterus to quiescence following spontaneous delivery.

This work was supported by The Wellcome Trust (grant no. 056285).