Potassium channels and uterine function

Brainard, Adam M.; Korovkina, Victoria P.; England, Sarah K.

doi:10.1016/j.semcdb.2007.05.008

Cited by 102 publications

(116 citation statements)

References 72 publications

(99 reference statements)

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“…It is possible that PKA-dependent uterine relaxation is mediated by other pathways, e.g. activation of potassium channels in myometrial cells [27,29].…”

Section: Discussionmentioning

confidence: 99%

Phosphorylation of proteins during human myometrial contractions: A phosphoproteomic approach

Hudson

Bernal

2017

Biochemical and Biophysical Research Communications

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General rightsThis document is made available in accordance with publisher policies. Please cite only the published version using the reference above. Full terms of use are available: http://www.bristol.ac.uk/pure/about/ebr-terms . Other yet unknown phosphorylation or de-phosphorylation events may contribute to myometrial contraction and relaxation. In this study we have performed a global phosphoproteomic analysis of human myometrial tissue using tandem mass tagging to detect changes in the phosphorylation status of individual myometrial proteins during spontaneous and oxytocin-driven phasic contractions. We were able to detect 22 individual phosphopeptides whose relative ratio changed (fold > 2 or < 0.5) in response to spontaneous or oxytocin-stimulated contraction.The most significant changes in phosphorylation were to MYLK on serine 1760, a site associated with reductions in calmodulin binding and subsequent kinase activity.Phosphorylated MYLK (ser1760) increased significantly during spontaneous (9.83 ± 3.27 fold, P < 0.05) and oxytocin -induced (18.56 ± 8.18 fold, P < 0.01) contractions and we were able to validate these data using immunoblotting. Pathway analysis suggested additional proteins involved in calcium signalling, cGMP-PRKG signalling, adrenergic signalling and oxytocin signalling were also phosphorylated during contractions. This study demonstrates that a global phosphoproteomic analysis of myometrial tissue is a sensitive approach to detect changes in the phosphorylation of proteins during myometrial contractions, and provides a platform for further validation of these changes and for identification of their functional significance.

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“…It is possible that PKA-dependent uterine relaxation is mediated by other pathways, e.g. activation of potassium channels in myometrial cells [27,29].…”

Section: Discussionmentioning

confidence: 99%

Phosphorylation of proteins during human myometrial contractions: A phosphoproteomic approach

Hudson

Bernal

2017

Biochemical and Biophysical Research Communications

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“…The factors regulating these painful contractions during pregnancy and labor are poorly understood. K ATP channel activation has been shown to decrease the uterine tone and this is a target for the inhibition of uterine activity in the treatment of preterm labor (Piper et al 1990, Brainard et al 2007. K ATP channels are composed of two different subunits: SURs and Kir 6.x .…”

Section: Discussionmentioning

confidence: 99%

“…The opening of these channels results in an outward flow of K C , drawing the cell membrane potential closer to the K C equilibrium potential and thereby reducing cellular excitability and contractility (Khan et al 2001). There are several types of K C channels: the large-conductance calcium-and voltage-sensitive K C channel (BK Ca channel), the ATP-sensitive K C channel (K ATP channel), the Shaker-like voltage-gated K C channel (Kv channel), and small-conductance calcium-sensitive K C channels (SK channel; Brainard et al 2007). K ATP channels were first discovered in cardiac myocytes (Noma 1983) and later in many other tissues including pancreatic b-cells, skeletal muscle, smooth muscle, brain, pituitary, kidney, and mitochondria.…”

Section: Introductionmentioning

confidence: 99%

Ontogeny of sulfonylurea-binding regulatory subunits of KATP channels in the pregnant rat myometrium

Lovasz¹,

Ducza²,

Gáspár³

et al. 2011

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ATP-sensitive potassium channels (K ATP channels) are composed of sulfonylurea receptors (SURs) and potassium inward rectifiers (Kir 6.x ) that assemble to form a large octameric channel. This study was designed to examine the expression and role of sulfonylureabinding regulatory subunits 1 (SUR1 (ABCC8)) and 2 (SUR2 (ABCC9)) of the K ATP channels in the pregnant rat myometrium with particular regard to the contractility. RT-PCR and western blot analyses were performed to detect the presence of SUR1 and SUR2. The SUR1 levels were markedly increased in the early stages of pregnancy. The highest level was detected on day 6 of pregnancy, whereas in the late stages, the levels of SUR1 were significantly decreased. The SUR2 level remained unchanged throughout pregnancy. The SUR non-selective diazoxide and the SUR2-selective pinacidil inhibited oxytocin-induced contractions. Glibenclamide, a K ATP channel blocker, antagonized both pinacidil-and diazoxide-induced relaxations. It was established that SURs are responsible for pharmacological reactivity of K ATP channel openers. We conclude that both SURs are involved in the K ATP channel in the pregnant rat myometrium. It may further be concluded that 'pinacidil-like' K ATP channel openers may be of therapeutic relevance as tocolytic agents in the future.

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“…These BK Ca channels are voltage-and Ca 2ϩ -sensitive and have been described to have a profound effect on myometrial relaxation during midgestation in rodents. BK Ca channels have been extensively studied in myometrium because of their relatively high density and the significant repolarizing current induced by the considerable ϳ200-to 300-pS conductance of these channels (10). Another category of ion channels, voltage-gated K ϩ (K v ) channels, are widely expressed in uterine smooth muscle cells, and their activation has been reported to contribute to basal uterine tone prior to labor (36).…”

mentioning

confidence: 99%

TREK-1 currents in smooth muscle cells from pregnant human myometrium

Heyman

Cowles

Barnett

et al. 2013

American Journal of Physiology-Cell Physiology

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The mechanisms governing maintenance of quiescence during pregnancy remain largely unknown. The current study characterizes a stretch-activated, tetraethylammoniuminsensitive K ϩ current in smooth muscle cells isolated from pregnant human myometrium. This study hypothesizes that these K ϩ currents can be attributed to TREK-1 and that upregulation of this channel during pregnancy assists with the maintenance of a negative cell membrane potential, conceivably contributing to uterine quiescence until full term. The results of this study demonstrate that, in pregnant human myometrial cells, outward currents at 80 mV increased from 4.8 Ϯ 1.5 to 19.4 Ϯ 7.5 pA/pF and from 3.0 Ϯ 0.8 to 11.8 Ϯ 2.7 pA/pF with application of arachidonic acid (AA) and NaHCO 3, respectively, causing intracellular acidification. Similarly, outward currents were inhibited following application of 10 M fluphenazine by 51.2 Ϯ 9.8% after activation by AA and by 73.9 Ϯ 4.2% after activation by NaHCO3. In human embryonic kidney (HEK-293) cells stably expressing TREK-1, outward currents at 80 mV increased from 91.0 Ϯ 23.8 to 247.5 Ϯ 73.3 pA/pF and from 34.8 Ϯ 8.9 to 218.6 Ϯ 45.0 pA/pF with application of AA and NaHCO3, respectively. Correspondingly, outward currents were inhibited 89.5 Ϯ 2.3% by 10 M fluphenazine following activation by AA and by 91.6 Ϯ 3.4% following activation by NaHCO3. Moreover, currents in human myometrial cells were activated by stretch and were reduced by transfection with small interfering RNA or extracellular acidification. Understanding gestational regulation of expression and gating of TREK-1 channels could be important in determining appropriate maintenance of uterine quiescence during pregnancy.

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Potassium channels and uterine function

Cited by 102 publications

References 72 publications

Phosphorylation of proteins during human myometrial contractions: A phosphoproteomic approach

Phosphorylation of proteins during human myometrial contractions: A phosphoproteomic approach

Ontogeny of sulfonylurea-binding regulatory subunits of KATP channels in the pregnant rat myometrium

TREK-1 currents in smooth muscle cells from pregnant human myometrium

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