Abstract:
: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.
journal_name
Nat Communjournal_title
Nature communicationsauthors
Parkington HC,Stevenson J,Tonta MA,Paul J,Butler T,Maiti K,Chan EC,Sheehan PM,Brennecke SP,Coleman HA,Smith Rdoi
10.1038/ncomms5108subject
Has Abstractpub_date
2014-06-17 00:00:00pages
4108issn
2041-1723pii
ncomms5108journal_volume
5pub_type
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