Role of mitochondria in contraction and pacemaking in the mouse uterus
- 27 October 2010
- journal article
- research article
- Published by Wiley in British Journal of Pharmacology
- Vol. 161 (6), 1375-1390
- https://doi.org/10.1111/j.1476-5381.2010.00949.x
Abstract
Uterine spontaneous contraction and pacemaking are poorly understood. This study investigates the role of the mitochondrial Ca(2+) store in uterine activity. 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. 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. 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.This publication has 56 references indexed in Scilit:
- Guide to Receptors and Channels (GRAC), 4th editionBritish Journal of Pharmacology, 2009
- Inositol trisphosphate‐dependent Ca2+ stores and mitochondria modulate slow wave activity arising from the smooth muscle cells of the guinea pig prostate glandBritish Journal of Pharmacology, 2009
- Smooth muscle cell calcium activation mechanismsJournal Of Physiology-London, 2008
- Role of mitochondria in modulation of spontaneous Ca2+ waves in freshly dispersed interstitial cells of Cajal from the rabbit urethraJournal Of Physiology-London, 2008
- Role of Ca2+ entry and Ca2+ stores in atypical smooth muscle cell autorhythmicity in the mouse renal pelvisBritish Journal of Pharmacology, 2007
- Potassium channels and uterine functionSeminars in Cell & Developmental Biology, 2007
- Structure and organization of interstitial cells of Cajal in the gastrointestinal tractJournal Of Physiology-London, 2006
- Structural and functional features and significance of the physical linkage between ER and mitochondriaThe Journal of cell biology, 2006
- The mitochondrial calcium uniporter is a highly selective ion channelNature, 2004
- The Effects of 2-Aminoethoxydiphenyl Borate, a Novel Inositol 1,4,5-Trisphosphate Receptor Modulator on Myometrial ContractionsBiochemical and Biophysical Research Communications, 1999