Journal
JOURNAL OF CELL SCIENCE
Volume 121, Issue 1, Pages 75-85Publisher
COMPANY OF BIOLOGISTS LTD
DOI: 10.1242/jcs.014522
Keywords
smooth muscle; calcium; mitochondria; membrane potential
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Funding
- Wellcome Trust [078054/Z/05/Z] Funding Source: Medline
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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) P-3]-evoked Ca2+ release and prolonged the time required for restoration of [Ca2+](c) following activation of plasmalemmal Ca2+ currents (I-Ca).Ca2+ could be released from mitochondria immediately ( within 15 seconds) after a [Ca2+] c rise evoked by Ins(1,4,5)P-3 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 Ca2+ 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 [Ca2+](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.
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