Proceedings of The Physiological Society

University College Dublin (2009) Proc Physiol Soc 15, C23

Oral Communications

4-Aminopyridine sensitivity in human placental chorionic plate arteries

T. A. Mills1, E. J. Cowley1, S. L. Greenwood1, C. P. Sibley1, M. Wareing1

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

  • Figure 1: Scatter plot represents % change in baseline diameter of chorionic plate arteries in response to cumulative concentrations of 4-AP (N=8; line at median).

Voltage gated potassium channels (KV) alter vascular tone by effecting changes in membrane potential and regulating Ca2+ influx. Several KV channel subtypes are expressed in the fetoplacental vasculature, but the functionally important KV channels have not been identified [1, 2]. KV channel subtypes have different sensitivities to block by 4-aminopyridine (4-AP) and we showed previously that the basal tone of chorionic plate arteries was significantly increased by 1mM 4-AP [2]. Here, we test the hypothesis that different KV channel subtypes contribute to regulation of fetoplacental vascular tone by determining the sensitivity of chorionic plate artery (CPA) constriction to 4-AP, using pressure myography. Term placentas (N=8) were obtained post-delivery (vaginal or Caesarean section) from uncomplicated pregnancies. Biopsies were placed into ice-cold HCO3--buffered physiologic salt solution (PSS). CPAs were mounted on a pressure myograph, equilibrated for 30 minutes at an intraluminal pressure of 20mmHg (to reproduce pressure in vivo) with intraluminal flow (20μl/min; 37oC, 5%O2/5%CO2). Contraction was assessed with 120mM potassium solution (KPSS) and U46619 (10-10-2x10-6M) added to the bath. Post wash, a concentration response curve to 4-AP (1-5000µM) was performed. U46619 contraction (10-10-2x10-6M) was then assessed in the continued presence of 5000μM 4-AP. Baseline arterial diameters were 272±24μM. KPSS reduced baseline CPA diameters by 39±8%. 4-AP reduced baseline diameter of CPAs at concentrations above 5µM (Figure 1; *P<0.05 Wilcoxon Signed Rank Test). 4-AP did not affect maximum U46619 constriction at 10-6M (data not shown). In conclusion, 4-AP induced constriction of chorionic plate arteries at concentrations above 5μM, confirming and extending our previous observations that KV channels contribute to maintenance of chorionic plate arterial tone [2, 3]. Future studies with more specific blockers could address the contribution of 4-AP-sensitive KV channel subtypes to regulating fetoplacental vascular resistance and blood flow in normal and compromised pregnancies.

Where applicable, experiments conform with Society ethical requirements