The browser you are using is not supported by this website. All versions of Internet Explorer are no longer supported, either by us or Microsoft (read more here: https://www.microsoft.com/en-us/microsoft-365/windows/end-of-ie-support).

Please use a modern browser to fully experience our website, such as the newest versions of Edge, Chrome, Firefox or Safari etc.

Developmental regulation of smooth muscle contraction in the urinary bladder

På svenska

Author

  • Mari Ekman

Summary, in English

Smooth muscle cells in the urinary bladder are involved in the control of urine filling and emptying. We have used mice to study the contractile regulation of urinary bladder smooth muscle during the fetal period. We found that nerve-induced contractions are mainly dependent on muscarinic receptor activation in the newborn whereas adult bladders are equally dependent on muscarinic and purinergic receptor activation. Muscarinic receptor-induced contractions are due to activation of the M3 subtype in both adults and newborns. Activator calcium is mainly recruited from the extracellular space via L-type calcium channels in both adult and newborn tissue. The contractile machinery of the newborn’s bladder tissue is more sensitive to calcium which enables contractions at lower intracellular and extracellular calcium concentrations. Non-muscle myosin is contributing to the force development in the newborn but is not the cause for the increased calcium sensitivity. The increased calcium sensitivity is due to a lower phosphatase activity and a lower expression of the myosin light chain phosphatase subunit MYPT1. The contractions induced by muscarinic receptor agonists are characterized by increased phasic activity in the newborn. This activity is not dependent on K+ channels, calcium release from the sarcoplasmic reticulum or gap junctional transmission. Muscarinic receptor stimulation activates T-type calcium channels in the newborn bladder but not in the adult. The main sensitizing pathways, involving protein kinase C (PKC) and Rho-kinase, are established in the newborn tissue. The effects of PKC activation on muscarinic receptor-induced responses differ in newborn and adult tissue. The muscarinic receptor-induced response of the newborn is abolished in the presence of high PKC activation (using PDBu) whereas the response is potentiated in the adult. The phasic component of the response in the newborn bladder is particularly inhibited due to activation of PKC.

Publishing year

2008

Language

English

Publication/Series

Lund University Faculty of Medicine Doctoral Dissertation Series

Volume

2008:107

Document type

Dissertation

Publisher

Mari Ekman

Topic

  • Basic Medicine

Keywords

  • newborn
  • Rho-kinase
  • cellular signaling
  • muscarinic receptors
  • calcium sensitivity
  • protein kinase C
  • non-muscle myosin
  • myosin light chain phosphatase

Status

Published

Research group

  • Vascular Physiology
  • Cellular Biomechanics

ISBN/ISSN/Other

  • ISSN: 1652-8220
  • ISBN: 978-91-86059-60-6

Defence date

21 November 2008

Defence time

09:15

Defence place

Belfragesalen, BMC D15

Opponent

  • Christian Aalkjaer (Prof)