4 Biochemistry of myometrial contractility

Egarter, Christian; Husslein, P.

doi:10.1016/s0950-3552(05)80187-7

Cited by 48 publications

(22 citation statements)

References 32 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Relative acidifi cation at the myocyte membrane activating TREK-1 during gestation would fit with hyperpolarization of the membrane and decreased uterine activity. An abundance of www.chinaphar.com Buxton ILO et al Acta Pharmacologica Sinica npg arachidonic acid in pregnant myometrium [49] also would signal TREK-1 activation. Together, these infl uences may contribute to gestational uterine quiescence.…”

Section: Arachidonic Acid and Acidic Ph In Pregnancy Myometriummentioning

confidence: 99%

A role of stretch-activated potassium currents in the regulation of uterine smooth muscle contraction

Buxton

Heyman

et al. 2011

Acta Pharmacol Sin

View full text Add to dashboard Cite

Rates of premature birth are alarming and threaten societies and healthcare systems worldwide. Premature labor results in premature birth in over 50% of cases. Preterm birth accounts for three-quarters of infant morbidity and mortality. Children that survive birth before 34 weeks gestation often face life-long disability. Current treatments for preterm labor are wanting. No treatment has been found to be generally effective and none are systematically evaluated beyond 48 h. New approaches to the treatment of preterm labor are desperately needed. Recent studies from our laboratory suggest that the uterine muscle is a unique compartment with regulation of uterine relaxation unlike that of other smooth muscles. Here we discuss recent evidence that the mechanically activated 2-pore potassium channel, TREK-1, may contribute to contraction-relaxation signaling in uterine smooth muscle and that TREK-1 gene variants associated with human labor and preterm labor may lead to a better understanding of preterm labor and its possible prevention.

show abstract

Section: Arachidonic Acid and Acidic Ph In Pregnancy Myometriummentioning

confidence: 99%

A role of stretch-activated potassium currents in the regulation of uterine smooth muscle contraction

Buxton

Heyman

et al. 2011

Acta Pharmacol Sin

View full text Add to dashboard Cite

show abstract

“…chain kinase (MLCK) (12), leading to inhibition of the interaction between actin and myosin. Consequently, agonists that stimulate cAMP/PKA signaling generally produce smooth muscle relaxation.…”

Section: Figurementioning

confidence: 99%

“…Also important for myometrial activation are the proteins that make up the contractile apparatus, including the thick filament-associated protein smooth muscle myosin heavy chain (SM-MHC) and the thin filament-associated proteins α-SMA, calponin, and h-caldesmon (7,12). Actin and myosin are the principal interacting structural proteins that generate myocyte contractility.…”

Section: Introductionmentioning

confidence: 99%

Prostacyclin primes pregnant human myometrium for an enhanced contractile response in parturition

Fetalvero¹,

Zhang²,

Shyu³

et al. 2008

J. Clin. Invest.

View full text Add to dashboard Cite

An incomplete understanding of the molecular events that regulate the myometrial transition from the quiescent pregnant state to the active contractile state during labor has hindered the development of improved therapies for preterm labor. During myometrial activation, proteins that prime the smooth muscle for contraction are upregulated, allowing maximal responsiveness to contractile agonists and thereby producing strong phasic contractions. Upregulation of one such protein, COX-2, generates PGs that induce contractions. Intriguingly, the predominant myometrial PG produced just prior to labor is prostacyclin (PGI 2 ), a smooth muscle relaxant. However, here we have shown that activation of PGI 2 receptor (IP) upregulated the expression of several contractile proteins and the gap junction protein connexin 43 through cAMP/PKA signaling in human myometrial tissue in organ and cell culture. Functionally, these IP-dependent changes in gene expression promoted an enhanced contractile response to oxytocin in pregnant human myometrial tissue strips, which was inhibited by the IP antagonist RO3244794. Furthermore, contractile protein induction was dependent on the concentration and time of exposure to the PGI 2 analog iloprost and was blocked by both RO3244794 and PKA knockdown. We therefore propose that PGI 2 -mediated upregulation of contractile proteins and connexin 43 is a critical step in myometrial activation, allowing for a maximal contractile response. Our observations have important implications regarding activation of the myometrium prior to the onset of labor.

show abstract

“…Because of the polymodal control of TREK-1 activity, the channel is ideally suited for a role in regulating contractility of human myometrium over the many changes present during the course of human pregnancy. Changes in many of the factors that regulate TREK-1 channel activity, such as membrane stretch, AA, pH, nitric oxide, and others, could be experienced by uterine smooth muscle cells during pregnancy (3,21,38). Myocyte signaling domains may be acidic on the basis of their construction (4).…”

Section: Discussionmentioning

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

View full text Add to dashboard Cite

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.

show abstract

4 Biochemistry of myometrial contractility

Cited by 48 publications

References 32 publications

A role of stretch-activated potassium currents in the regulation of uterine smooth muscle contraction

A role of stretch-activated potassium currents in the regulation of uterine smooth muscle contraction

Prostacyclin primes pregnant human myometrium for an enhanced contractile response in parturition

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

Contact Info

Product

Resources

About