The Library
Alterations in gap junction connexin43/connexin45 ratio mediate a transition from quiescence to excitation in a mathematical model of the myometrium
Tools
Tools
Tools
Sheldon, Rachel E., Mashayamombe, Chipo, Shi, S. -Q., Garfield, R. E., Shmygol, Anatoly, Blanks, Andrew M. and Berg, Hugo van den (2014) Alterations in gap junction connexin43/connexin45 ratio mediate a transition from quiescence to excitation in a mathematical model of the myometrium. Journal of The Royal Society Interface, Volume 11 (Number 101). Article number 20140726. doi:10.1098/rsif.2014.0726 ISSN 1742-5689.
|
PDF
WRAP_0705082-ch-011014-sheldon_2014_voltagedependence.pdf - Accepted Version - Requires a PDF viewer. Download (3415Kb) | Preview |
Official URL: http://dx.doi.org/10.1098/rsif.2014.0726
Abstract
The smooth muscle cells of the uterus contract in unison during delivery. These cells achieve coordinated activity via electrical connections called gap junctions which consist of aggregated connexin proteins such as connexin43 and connexin45. The density of gap junctions governs the excitability of the myometrium (among other factors). An increase in gap junction density occurs immediately prior to parturition. We extend a mathematical model of the myometrium by incorporating the voltage-dependence of gap junctions that has been demonstrated in the experimental literature. Two functional subtypes exist, corresponding to systems with predominantly connexin43 and predominantly connexin45, respectively. Our simulation results indicate that the gap junction protein connexin45 acts as a negative modulator of uterine excitability, and hence, activity. A network with a higher proportion of connexin45 relative to connexin43 is unable to excite every cell. Connexin45 has much more rapid gating kinetics than connexin43 which we show limits the maximum duration of a local burst of activity. We propose that this effect regulates the degree of synchronous excitation attained during a contraction. Our results support the hypothesis that as labour approaches, connexin45 is downregulated to allow action potentials to spread more readily through the myometrium.
| Item Type: | Journal Article | ||||||
|---|---|---|---|---|---|---|---|
| Subjects: | Q Science > QM Human anatomy R Medicine > RG Gynecology and obstetrics |
||||||
| Divisions: | Faculty of Science, Engineering and Medicine > Research Centres > Molecular Organisation and Assembly in Cells (MOAC) Faculty of Science, Engineering and Medicine > Medicine > Warwick Medical School > Biomedical Sciences > Translational & Experimental Medicine > Reproductive Health ( - until July 2016) Faculty of Science, Engineering and Medicine > Research Centres > Warwick Systems Biology Centre Faculty of Science, Engineering and Medicine > Medicine > Warwick Medical School |
||||||
| Library of Congress Subject Headings (LCSH): | Uterus -- Contraction, Gap junctions (Cell biology), Connexins | ||||||
| Journal or Publication Title: | Journal of The Royal Society Interface | ||||||
| Publisher: | The Royal Society Publishing | ||||||
| ISSN: | 1742-5689 | ||||||
| Official Date: | 4 September 2014 | ||||||
| Dates: |
|
||||||
| Volume: | Volume 11 | ||||||
| Number: | Number 101 | ||||||
| Article Number: | Article number 20140726 | ||||||
| DOI: | 10.1098/rsif.2014.0726 | ||||||
| Status: | Peer Reviewed | ||||||
| Publication Status: | Published | ||||||
| Access rights to Published version: | Restricted or Subscription Access | ||||||
| Date of first compliant deposit: | 25 June 2016 | ||||||
| Date of first compliant Open Access: | 25 June 2016 | ||||||
| Related URLs: |
Request changes or add full text files to a record
Repository staff actions (login required)
 |
View Item |
Downloads
Downloads per month over past year
