{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T04:46:38Z","timestamp":1790138798660,"version":"4.0.1"},"reference-count":84,"publisher":"American Physiological Society","issue":"3","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American Journal of Physiology-Cell Physiology"],"published-print":{"date-parts":[[2012,8,1]]},"abstract":"<jats:p> Regulation of cytosolic Ca<jats:sup>2+<\/jats:sup> concentration ([Ca<jats:sup>2+<\/jats:sup>]<jats:sub>cyt<\/jats:sub>) in airway smooth muscle (ASM) is a key aspect of airway contractility and can be modulated by inflammation. Mitochondria have tremendous potential for buffering [Ca<jats:sup>2+<\/jats:sup>]<jats:sub>cyt<\/jats:sub>, helping prevent Ca<jats:sup>2+<\/jats:sup> overload, and modulating other intracellular events. Here, compartmentalization of mitochondria to different cellular regions may subserve different roles. In the present study, we examined the role of Ca<jats:sup>2+<\/jats:sup> buffering by mitochondria and mitochondrial Ca<jats:sup>2+<\/jats:sup> transport mechanisms in the regulation of [Ca<jats:sup>2+<\/jats:sup>]<jats:sub>cyt<\/jats:sub> in enzymatically dissociated human ASM cells upon exposure to the proinflammatory cytokines TNF-\u03b1 and IL-13. Cells were loaded simultaneously with fluo-3 AM and rhod-2 AM, and [Ca<jats:sup>2+<\/jats:sup>]<jats:sub>cyt<\/jats:sub> and mitochondrial Ca<jats:sup>2+<\/jats:sup> concentration ([Ca<jats:sup>2+<\/jats:sup>]<jats:sub>mito<\/jats:sub>) were measured, respectively, using real-time two-color fluorescence microscopy in both the perinuclear and distal, perimembranous regions of cells. Histamine induced a rapid increase in both [Ca<jats:sup>2+<\/jats:sup>]<jats:sub>cyt<\/jats:sub> and [Ca<jats:sup>2+<\/jats:sup>]<jats:sub>mito<\/jats:sub>, with a significant delay in the mitochondrial response. Inhibition of the mitochondrial Na<jats:sup>+<\/jats:sup>\/Ca<jats:sup>2+<\/jats:sup> exchanger (1 \u03bcM CGP-37157) increased [Ca<jats:sup>2+<\/jats:sup>]<jats:sub>mito<\/jats:sub> responses in perinuclear mitochondria but not distal mitochondria. Inhibition of the mitochondrial uniporter (1 \u03bcM Ru360) decreased [Ca<jats:sup>2+<\/jats:sup>]<jats:sub>mito<\/jats:sub> responses in perinuclear and distal mitochondria. CGP-37157 and Ru360 significantly enhanced histamine-induced [Ca<jats:sup>2+<\/jats:sup>]<jats:sub>cyt<\/jats:sub>. TNF-\u03b1 and IL-13 both increased [Ca<jats:sup>2+<\/jats:sup>]<jats:sub>cyt<\/jats:sub>, which was associated with decreased [Ca<jats:sup>2+<\/jats:sup>]<jats:sub>mito<\/jats:sub> in the case of TNF-\u03b1 but not IL-13. The effects of TNF-\u03b1 on both [Ca<jats:sup>2+<\/jats:sup>]<jats:sub>cyt<\/jats:sub> and [Ca<jats:sup>2+<\/jats:sup>]<jats:sub>mito<\/jats:sub> were affected by CGP-37157 but not by Ru360. Overall, these data demonstrate that in human ASM cells, mitochondria buffer [Ca<jats:sup>2+<\/jats:sup>]<jats:sub>cyt<\/jats:sub> after agonist stimulation and its enhancement by inflammation. The differential regulation of [Ca<jats:sup>2+<\/jats:sup>]<jats:sub>mito<\/jats:sub> in different parts of ASM cells may serve to locally regulate Ca<jats:sup>2+<\/jats:sup> fluxes from intracellular sources versus the plasma membrane as well as respond to differential energy demands at these sites. We propose that such differential mitochondrial regulation, and its disruption, may play a role in airway hyperreactivity in diseases such as asthma, where [Ca<jats:sup>2+<\/jats:sup>]<jats:sub>cyt<\/jats:sub> is increased. <\/jats:p>","DOI":"10.1152\/ajpcell.00414.2011","type":"journal-article","created":{"date-parts":[[2012,6,7]],"date-time":"2012-06-07T04:21:34Z","timestamp":1339042894000},"page":"C244-C256","source":"Crossref","is-referenced-by-count":57,"title":["Inflammation alters regional mitochondrial Ca<sup>2+<\/sup> in human airway smooth muscle cells"],"prefix":"10.1152","volume":"303","author":[{"given":"Philippe","family":"Delmotte","sequence":"first","affiliation":[{"name":"Department of Physiology and Biomedical Engineering, Mayo Clinic, Rochester, Minnesota; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Binxia","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology, Mayo Clinic, Rochester, Minnesota"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael A.","family":"Thompson","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology, Mayo Clinic, Rochester, Minnesota"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christina M.","family":"Pabelick","sequence":"additional","affiliation":[{"name":"Department of Physiology and Biomedical Engineering, Mayo Clinic, Rochester, Minnesota; and"},{"name":"Department of Anesthesiology, Mayo Clinic, Rochester, Minnesota"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Y. 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