Oral Presentation Annual Meetings of the Endocrine Society of Australia and Society for Reproductive Biology and Australia and New Zealand Bone and Mineral Society 2016

Potassium channels in dysfunctional human labour (#207)

Helena C Parkington 1 , Mary A Tonta 1 , Janet Stevenson 2 , Crystal Goundar 1 , Penelope M Sheehan 2 , Harold A Coleman 1 , Shaun P Brennecke 3
  1. Department of Physiology, Monash University, CLAYTON, VIC, Australia
  2. Department of Perinatal Medicine, Royal Women's Hospital, Melbourne, Victoria, Australia
  3. Department of Obstetrics and Gynecology, University of Melbourne, Melbourne, Victoria, Australia

Strong labour contractions require calcium influx through voltage-gated calcium channels. Thus, myometrial smooth muscle membrane potential is critical for good labour progress. Dysfunctional labour (DL) is a significant problem in the labour ward, and is the most common indication for caesarean delivery. We recently discovered a marked excessive negative membrane potential in myometrium of both lean and obese DL women. We hypothesized that this negative membrane potential is caused by excessive activity and/or levels of K+ channels, the resulting negativity suppressed opening of calcium channels resulting in weak contraction and DL.

Electrophysiology was used to record membrane potential and K+ channel activity in term not-in-labour (NIL) and in labour (IL) myometrium. K+ channel protein levels were determined using western blotting.

Myometrial strips from women progressing well IL had spontaneous contractions (n=7). DL strips did not contract spontaneously (n=9), although contraction could be achieved using experimental depolarizations. Resting membrane potential in myometrium from normally progressing women NIL was -58±1mV (n=17) and IL was -58±1mV (n=7). DL myometrium was significantly more negative IL (-73±2mV, n=9). Blockade of KV7 channels, using XE-991, returned resting potential to normal levels (-61±2mV) in high negative DL myometrium. Levels of KV7.1 protein did not change in myometrium from normally progressing women before versus in labour, but was significantly increased in DL (21.2±2.4, n=5) versus normal progress IL (11.9±1.6, n=5, p=0.02). Levels of KV7.4 protein were also significantly increased in myometrium from DL IL women (1.18±0.14, n=5) versus normally progressing labour (0.26±0.04, n=5, p=0.0008). In acutely isolated myometrial cells the KV7 current (at 20mV) was enhanced in IL DL (6.1±1.1pA/pF) versus normal progress (2.5±0.5pA/pF, p=0.02). In DL myometrium, depolarization evoked by oxytocin (10nM) was 8±2mV, insufficient to overcome the negativity and so did not cause contraction. Dysfunction of KV7 channels is a major contributor to DL in women.