{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,16]],"date-time":"2026-03-16T11:42:59Z","timestamp":1773661379401,"version":"3.50.1"},"reference-count":54,"publisher":"American Physiological Society","issue":"4","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American Journal of Physiology-Cell Physiology"],"published-print":{"date-parts":[[2005,10]]},"abstract":"<jats:p> In the present study, we used laser scanning confocal microscopy in combination with fluorescent indicator dyes to investigate the effects of nitric oxide (NO) produced endogenously by stimulation of the mitochondria-specific NO synthase (mtNOS) or applied exogenously through a NO donor, on mitochondrial Ca<jats:sup>2+<\/jats:sup> uptake, membrane potential, and gating of mitochondrial permeability transition pore (PTP) in permeabilized cultured calf pulmonary artery endothelial (CPAE) cells. Higher concentrations (100\u2013500 \u03bcM) of the NO donor spermine NONOate (Sper\/NO) significantly reduced mitochondrial Ca<jats:sup>2+<\/jats:sup> uptake and Ca<jats:sup>2+<\/jats:sup> extrusion rates, whereas low concentrations of Sper\/NO (&lt;100 \u03bcM) had no effect on mitochondrial Ca<jats:sup>2+<\/jats:sup> levels ([Ca<jats:sup>2+<\/jats:sup>]<jats:sub>mt<\/jats:sub>). Stimulation of mitochondrial NO production by incubating cells with 1 mM l-arginine also decreased mitochondrial Ca<jats:sup>2+<\/jats:sup> uptake, whereas inhibition of mtNOS with 10 \u03bcM l- N<jats:sup>5<\/jats:sup>-(1-iminoethyl)ornithine resulted in a significant increase of [Ca<jats:sup>2+<\/jats:sup>]<jats:sub>mt<\/jats:sub>. Sper\/NO application caused a dose-dependent sustained mitochondrial depolarization as revealed with the voltage-sensitive dye tetramethylrhodamine ethyl ester (TMRE). Blocking mtNOS hyperpolarized basal mitochondrial membrane potential and partially prevented Ca<jats:sup>2+<\/jats:sup>-induced decrease in TMRE fluorescence. Higher concentrations of Sper\/NO (100\u2013500 \u03bcM) induced PTP opening, whereas lower concentrations (&lt;100 \u03bcM) had no effect. The data demonstrate that in calf pulmonary artery endothelial cells, stimulation of mitochondrial Ca<jats:sup>2+<\/jats:sup> uptake can activate NO production in mitochondria that in turn can modulate mitochondrial Ca<jats:sup>2+<\/jats:sup> uptake and efflux, demonstrating a negative feedback regulation. This mechanism may be particularly important to protect against mitochondrial Ca<jats:sup>2+<\/jats:sup> overload under pathological conditions where cellular [NO] can reach very high levels. <\/jats:p>","DOI":"10.1152\/ajpcell.00011.2005","type":"journal-article","created":{"date-parts":[[2005,5,19]],"date-time":"2005-05-19T00:24:34Z","timestamp":1116462274000},"page":"C836-C845","source":"Crossref","is-referenced-by-count":44,"title":["Modulation of mitochondrial Ca<sup>2+<\/sup> by nitric oxide in cultured bovine vascular endothelial cells"],"prefix":"10.1152","volume":"289","author":[{"given":"Elena N.","family":"Dedkova","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lothar A.","family":"Blatter","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"24","reference":[{"key":"R1","doi-asserted-by":"crossref","unstructured":"Akaike T, Yoshida M, Miyamoto Y, Sato K, Kohno M, Sasamoto K, Miyazaki K, Ueda S, and Maeda H. 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