{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T15:42:43Z","timestamp":1791214963735,"version":"4.1.0"},"reference-count":46,"publisher":"Society for Neuroscience","issue":"15","license":[{"start":{"date-parts":[[2015,10,15]],"date-time":"2015-10-15T00:00:00Z","timestamp":1444867200000},"content-version":"vor","delay-in-days":183,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-sa\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J. Neurosci."],"published-print":{"date-parts":[[2015,4,15]]},"abstract":"<jats:p>As auxiliary subunits of voltage-gated Ca<jats:sup>2+<\/jats:sup>channels, the \u03b1<jats:sub>2<\/jats:sub>\u03b4 proteins modulate membrane trafficking of the channels and their localization to specific presynaptic sites. Following nerve injury, upregulation of the \u03b1<jats:sub>2<\/jats:sub>\u03b4-1 subunit in sensory dorsal root ganglion neurons contributes to the generation of chronic pain states; however, very little is known about the underlying molecular mechanisms. Here we show that the increased expression of \u03b1<jats:sub>2<\/jats:sub>\u03b4-1 in rat sensory neurons leads to prolonged Ca<jats:sup>2+<\/jats:sup>responses evoked by membrane depolarization. This mechanism is coupled to Ca<jats:sub>V<\/jats:sub>2.2 channel-mediated responses, as it is blocked by a \u03c9-conotoxin GVIA application. Once initiated, the prolonged Ca<jats:sup>2+<\/jats:sup>transients are not dependent on extracellular Ca<jats:sup>2+<\/jats:sup>and do not require Ca<jats:sup>2+<\/jats:sup>release from the endoplasmic reticulum. The selective inhibition of mitochondrial Ca<jats:sup>2+<\/jats:sup>uptake demonstrates that \u03b1<jats:sub>2<\/jats:sub>\u03b4-1-mediated prolonged Ca<jats:sup>2+<\/jats:sup>signals are buffered by mitochondria, preferentially activated by Ca<jats:sup>2+<\/jats:sup>influx through Ca<jats:sub>V<\/jats:sub>2.2 channels. Thus, by controlling channel abundance at the plasma membrane, the \u03b1<jats:sub>2<\/jats:sub>\u03b4-1 subunit has a major impact on the organization of depolarization-induced intracellular Ca<jats:sup>2+<\/jats:sup>signaling in dorsal root ganglion neurons.<\/jats:p>","DOI":"10.1523\/jneurosci.3997-14.2015","type":"journal-article","created":{"date-parts":[[2015,4,15]],"date-time":"2015-04-15T16:37:33Z","timestamp":1429115853000},"page":"5891-5903","source":"Crossref","is-referenced-by-count":50,"title":["The Upregulation of \u03b1<sub>2<\/sub>\u03b4-1 Subunit Modulates Activity-Dependent Ca<sup>2+<\/sup>Signals in Sensory Neurons"],"prefix":"10.1523","volume":"35","author":[{"given":"Marianna","family":"D'Arco","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wojciech","family":"Margas","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John 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