Proceedings of The Physiological Society

University of Oxford (2011) Proc Physiol Soc 23, PC239

Poster Communications

Effect of KV7 activators on chorionic plate arterial tone: A functional role for KV7 channels in the human placental vasculature?

T. A. Mills1, S. L. Greenwood1, C. P. Sibley1, M. Wareing1

1. Maternal and Fetal Health Research Centre, The University of Manchester, Manchester, United Kingdom.

KV7 channels, a subfamily of voltage-gated potassium channels, may be potentially important contributors to regulation of vascular tone in human systemic arteries [1]. Previously we demonstrated that pharmacological KV7 channel manipulation modifies the reactivity of placental chorionic plate arteries (CPAs) [2]. These data support a role for KV7 channels in regulating fetoplacental resistance artery tone but the functionally important subtypes have yet to be identified. Here, we assess the responses of CPA’s to structurally distinct KV7 channel openers. Methods: Term placentas (N=14) were obtained post delivery (vaginal or caesarean section), following uncomplicated pregnancies. Biopsies were placed into ice-cold HCO3--buffered physiologic salt solution (PSS). CPA’s were mounted on a wire myograph, normalized at 0.9L5.1KPa(≈20mmHg) and equilibrated (37oC; 20 min in 5%O2 / 5%CO2 ≈ 7% O2). Contractile responses were initially assessed with PSS containing 120mM potassium chloride (KPSS). Post wash, arteries were pre-constricted with arginine vasopressin (AVP; 10-8 M) and exposed to retigabine or S-1 acrylamide (KV7 openers; 10-9 -10-4M) and responses compared with diluent-treated controls (dimethylsulphoxide DMSO; maximum final concentration 1%). Experiments were repeated following pre-constriction with 80mM KPSS. Results: Baseline arterial diameters were 326±17μm (mean±SEM). AVP (10-8M) produced sustained constriction of CPAs. Retigabine (an anticonvulsant for use in the treatment of epilepsy) and S-1 acrylamide induced dose-dependent relaxation in CPAs, compared to diluent treated controls (p<0.05, 2 way ANOVA). S-1 acrylamide induced greater relaxation of vessels pre-constricted with AVP than retigabine (p<0.05, 2 way ANOVA mean±SEM; by 66±15% vs 45±14% (maximum relaxation expressed as a percentage of AVP constriction in controls), respectively. Retigabine and S-1 acrylamide relaxed arteries pre-constricted with 80mM KPSS. Conclusion: Pre-constricted CPAs relaxed in response to two structurally distinct KV7 channel openers. S-1 acrylamide is reported to have a preferential effect on KV7.4 channels [3]and retigabine on KV7.2-5 channels [4]; therefore our data suggest that KV7.4 and /or on KV7.2,3,5 channels could contribute to vascular tone regulation of CPA’s. In support of this proposal, we have previously localized KV7.4 channel protein to the CPA endothelium and smooth muscle. Further studies will examine a possible role for altered KV7.4 expression or function in the increased fetoplacental vascular resistance characteristic of fetal growth restriction.

Where applicable, experiments conform with Society ethical requirements