Journal article
Role of mitochondria in contraction and pacemaking in the mouse uterus
British Journal of Pharmacology, Vol.161(6), pp.1375-1390
2010
Abstract
BACKGROUND AND PURPOSE Uterine spontaneous contraction and pacemaking are poorly understood. This study investigates the role of the mitochondrial Ca 2+ store in uterine activity.EXPERIMENTAL APPROACH We investigated the effects of mitochondrial and sarco-endoplasmic reticulum (SER) inhibitors on contraction, membrane potential (Vm) and cytosolic Ca 2+ concentration ([Ca 2+] c) in longitudinal smooth muscle of the mouse uterus.KEY RESULTS The mitochondrial agents rotenone, carbonylcyanide-3-chlorophenylhydrazone (CCCP), 7-chloro-5-(2-chlorophenyl)-1,5-dihydro-4,1-benzothiazepin-2(3H)-one (CGP37157) and kaempferol decreased the force of contractions. The ATP synthase inhibitor oligomycin had no significant effect. The effects of these agents were compared with those of SER inhibitors cyclopiazonic acid (CPA), 2-amino ethoxyphenylborate (2-APB) and caffeine. All agents, except CPA and oligomycin, decreased contractile force. CPA and CCCP transiently increased contraction frequency, which returned to control levels, whereas rotenone, CGP37157, kaempferol and 2-APB decreased frequency and caffeine had no significant effect. Application of the mitochondrial agents when CPA functionally inhibited stores did not change contraction frequency but, with the exception of kaempferol, decreased force. CCCP caused depolarization and maintained increase in [Ca 2+] c or depolarization/transient hyperpolarization and transient increase in [Ca 2+] c for oestrus and di-oestrus tissues respectively. Rotenone caused hyperpolarization and maintained increase in [Ca 2+] c. CGP37157 and kaempferol caused hyperpolarization but no measurable change in [Ca 2+] c. Application of a range of K + channel blockers indicated a role of Ca 2+-activated K + (K Ca) channels in the CCCP- and CGP37157-induced actions.CONCLUSIONS AND IMPLICATIONS Mitochondria have a modulatory role on uterine contractions, with mitochondrial inhibition reducing contraction amplitude and pacemaker frequency by changes in Vm, [Ca 2+] c and/or Ca 2+ influx. © 2010 The Authors. British Journal of Pharmacology © 2010 The British Pharmacological Society.
Details
- Title
- Role of mitochondria in contraction and pacemaking in the mouse uterus
- Authors
- F Gravina (Author) - University of NewcastleH Parkington (Author) - Monash UniversityK Kerr (Author) - University of NewcastleR De Oliveira (Author) - University of NewcastleP Jobling (Author) - University of NewcastleH Coleman (Author) - Monash UniversityShaun L Sandow (Author) - University of New South WalesM Davies (Author) - Monash UniversityM Imtiaz (Author) - University of Calgary, CanadaD Van Helden (Author) - University of Newcastle
- Publication details
- British Journal of Pharmacology, Vol.161(6), pp.1375-1390
- Publisher
- John Wiley & Sons Ltd.
- Date published
- 2010
- DOI
- 10.1111/j.1476-5381.2010.00949.x
- ISSN
- 0007-1188
- Organisation Unit
- School of Health - Biomedicine; University of the Sunshine Coast, Queensland; School of Health and Sport Sciences - Legacy; School of Health and Behavioural Sciences - Legacy
- Language
- English
- Record Identifier
- 99448743002621
- Output Type
- Journal article
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