Diminished hERG K+ channel activity facilitates strong human labour contractions but is dysregulated in obese women

Human ether-a-go-go-related gene (hERG) potassium channels determine cardiac action potential and contraction duration. Human uterine contractions are underpinned by an action potential that also possesses an initial spike followed by prolonged depolarization. Here we show that hERG channel proteins...

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Bibliographic Details
Published in:Nature communications 2014-06, Vol.5 (1), p.4108-4108, Article 4108
Main Authors: Parkington, Helena C, Stevenson, Janet, Tonta, Mary A, Paul, Jonathan, Butler, Trent, Maiti, Kaushik, Chan, Eng-Cheng, Sheehan, Penelope M, Brennecke, Shaun P, Coleman, Harold A, Smith, Roger
Format: Article
Language:English
Subjects:
Action Potentials - physiology
Adult
Blotting, Western
Body Mass Index
Ether-A-Go-Go Potassium Channels - metabolism
Female
Humans
Membrane Potentials
Myometrium - metabolism
Obesity - metabolism
Obesity - physiopathology
Patch-Clamp Techniques
Potassium Channels, Voltage-Gated - metabolism
Statistics, Nonparametric
Uterine Contraction - metabolism
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Summary:Human ether-a-go-go-related gene (hERG) potassium channels determine cardiac action potential and contraction duration. Human uterine contractions are underpinned by an action potential that also possesses an initial spike followed by prolonged depolarization. Here we show that hERG channel proteins (α-conducting and β-inhibitory subunits) and hERG currents exist in isolated patch-clamped human myometrial cells. We show that hERG channel activity suppresses contraction amplitude and duration before labour, thereby facilitating quiescence. During established labour, expression of β-inhibitory protein is markedly enhanced, resulting in reduced hERG activity that is associated with an increased duration of uterine action potentials and contractions. Thus, changes in hERG channel activity contribute to electrophysiological mechanisms that produce contractions during labour. We also demonstrate that this system fails in women with elevated BMI, who have enhanced hERG activity as a result of low β-inhibitory protein expression, which likely contributes to the weak contractions and poor labour outcomes observed in many obese women necessitating caesarean delivery.
ISSN:2041-1723
2041-1723
DOI:10.1038/ncomms5108