Please use this identifier to cite or link to this item: http://hdl.handle.net/1959.13/932639

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Title
Role of mitochondria in contraction and pacemaking in the mouse uterus
Author/Creator
Gravina, F. S.;  Parkington, H. C.;  Kerr, K. P.;  De Oliveira, R. B. de;  Jobling, P.;  Coleman, H. A.;  Sandow, S. L.;  Davies, M. M.;  Imtiaz, M. S.;  van Helden, D. F.
Institution
The University of Newcastle. Faculty of Health, School of Biomedical Sciences and Pharmacy
Description
Background and purpose: Uterine spontaneous contraction and pacemaking are poorly understood. This study investigates the role of the mitochondrial Ca²⁺ 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 Ca²⁺ concentration ([Ca²⁺]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 [Ca²⁺]c or depolarization/transient hyperpolarization and transient increase in [Ca²⁺]c for oestrus and di-oestrus tissues respectively. Rotenone caused hyperpolarization and maintained increase in [Ca²⁺]c. CGP37157 and kaempferol caused hyperpolarization but no measurable change in [Ca²⁺]c. Application of a range of K⁺ channel blockers indicated a role of Ca²⁺-activated K⁺ (KCa) 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, [Ca²⁺]c and/or Ca²⁺ influx.
Relation
British Journal of Pharmacology Vol. 161, Issue 6, p. 1375-1390
Publisher Link
http://dx.doi.org/10.1111/j.1476-5381.2010.00949.x
Date
2010
Publisher
John Wiley & Sons
Keyword(s)
uterus;  mitochondria;  spontaneous contractions;  pacemaking
Resource Type
journal article
Identifier
http://hdl.handle.net/1959.13/932639
Identifier
ISSN:0007-1188
Reviewed
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Subject
"British Journal of Pharmacology"
 
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