The mitochondrial membrane potential and Ca2+ oscillations in smooth muscle.
Ca2+ uptake by mitochondria might both modulate the cytosolic Ca2+ concentration ([Ca2+]c) and depolarize the mitochondrial membrane potential (delta Psi m) to limit ATP production. To investigate how physiological Ca2+ signaling might affect energy production, delta Psi m was examined during Ca2+ oscillations in smooth muscle cells. In single, voltage-clamped smooth muscle cells, inhibition of mitochondrial Ca2+ accumulation inhibited inositol (1,4,5)-trisphosphate [Ins(1,4,5)P3]-evoked Ca2+ release and prolonged the time required for restoration of [Ca2+]c following activation of plasmalemmal Ca2+ currents (ICa). Ca2+ could be released from mitochondria immediately (within 15 seconds) after a [Ca2+]c rise evoked by Ins(1,4,5)P3 or ICa. Despite this evidence of mitochondrial Ca2+ accumulation, no change in delta Psi m was observed during single or repetitive [Ca2+]c oscillations evoked by these conditions. Occasionally, spontaneous, repetitive, persistent Ca 2+ oscillations were observed. In these cases, mitochondria displayed stochastic delta Psi m depolarizations, which were independent both of events in neighboring mitochondria and of the timing of the [Ca 2+]c oscillations themselves. Such delta Psi m depolarizations could be mimicked by increased exposure to either fluorescence excitation light or the delta Psi m-sensitive dye tetramethylrhodamine ethyl ester (TMRE) and were inhibited by antioxidants (ascorbic acid, catalase, Trolox and TEMPO) or the mitochondrial permeability transition pore (mPTP)-inhibitor cyclosporin A (CsA). Individual mitochondria within smooth muscle cells might depolarize during repetitive Ca2+ oscillations or during oxidative stress but not during the course of single [Ca2+]c transients evoked by Ca2+ influx or store release.
Chalmers
Susan
S
Strathclyde Institute of Pharmacy and Biomedical Sciences, University of Strathclyde, John Arbuthnott Building, 27 Taylor Street, Glasgow, G4 0NR, UK.
McCarron
John G
JG
D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism; D020013:Calcium Signaling / Q000187:drug effects; D016572:Cyclosporine / Q000494:pharmacology; D006168:Guinea Pigs; D015544:Inositol 1,4,5-Trisphosphate / Q000502:physiology; D008297:Male; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D008931:Mitochondria, Muscle / Q000000981:diagnostic imaging / Q000187:drug effects / Q000502:physiology*; D009130:Muscle, Smooth / Q000166:cytology / Q000000981:diagnostic imaging / Q000502:physiology*; D009942:Organometallic Compounds / Q000378:metabolism; D053038:Quorum Sensing; D011877:Radionuclide Imaging
D000975:Antioxidants; D009942:Organometallic Compounds; C110932:tetramethyl rhodamine ethyl ester; D016572:Cyclosporine; D015544:Inositol 1,4,5-Trisphosphate; D002118:Calcium