title: Oxytocin depolarizes mitochondria in isolated myometrial cells.
abstract: Oxytocin is known to play important roles in uterine contractions, mediated at least in part by increasing intracellular Ca(2+) concentration ([Ca(2+)](i)), through enhancing extracellular Ca(2+) entry and Ca(2+) release from the sarcoplasmic reticulum, processes that are intimately linked with mitochondria. This study examined the effects of oxytocin on mitochondrial function. This was achieved by measuring the ratiometric JC-1 fluorescence signal in isolated myometrial cells, which provides a relative measure of the mitochondrial membrane potential (ψ(m)), and also by loading the cells with Oregon Green BAPTA-AM to examine changes in [Ca(2+)](i). Oxytocin (1 nm) depolarized the ψ(m) to 73.8 ± 3.7% of the control value (P < 0.05; perfused for 11 min) and also caused a transient increase in [Ca(2+)](i). The depolarization of mitochondrial membrane potential was effectively reversed by 2-aminoethoxydiphenyl borate, nifedipine, Ca(2+)-free solution or oligomycin, with the ratiometric JC-1 fluorescence signal becoming no different from the control value in all cases (i.e. P > 0.05). The reduction in ψ(m) is likely to occur at least in part through the oxytocin-induced increase in [Ca(2+)](i), causing enhanced mitochondrial uptake of Ca(2+) and resultant dissipation of the mitochondrial electrochemical gradient. ATP synthase is also stimulated, which would further contribute to a decrease in ψ(m).
authors.affiliation: School of Biomedical Sciences & Pharmacy, University of Newcastle, University Drive, Callaghan, NSW 2308, Australia.
authors.forename: F S
authors.initials: FS
authors.lastname: Gravina
authors.forename: P
authors.initials: P
authors.lastname: Jobling
authors.forename: K P
authors.initials: KP
authors.lastname: Kerr
authors.forename: R B
authors.initials: RB
authors.lastname: de Oliveira
authors.forename: H C
authors.initials: HC
authors.lastname: Parkington
authors.forename: D F
authors.initials: DF
authors.lastname: van Helden
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism*; D005260:Female; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D051379:Mice; D008931:Mitochondria, Muscle / Q000187:drug effects*; D009215:Myometrium / Q000502:physiology; D009840:Oligomycins / Q000494:pharmacology; D010121:Oxytocin / Q000494:pharmacology*; D011189:Potassium Chloride / Q000494:pharmacology; D011247:Pregnancy
chemical_list: D009840:Oligomycins; D010121:Oxytocin; D011189:Potassium Chloride; D002118:Calcium