Intracellular calcium dynamics induced by Propofol and Nicotine - Observations using the intracellular organelle calcium indicator CEPIA (calcium-measuring organelle-entrapped protein indicators)

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  • Soma Noguchi
    Dept. of Mol. & Pharmacol. Neurosci., Grad. Sch. of Biomed. & Health Sci., Hiroshima Univ.
  • Wada Kazuki
    Dept. of Mol. & Pharmacol. Neurosci., Grad. Sch. of Biomed. & Health Sci., Hiroshima Univ.
  • Harada Kana
    Dept. of Mol. & Pharmacol. Neurosci., Grad. Sch. of Biomed. & Health Sci., Hiroshima Univ.
  • Tanaka Shigeru
    Dept. of Mol. & Pharmacol. Neurosci., Grad. Sch. of Biomed. & Health Sci., Hiroshima Univ.
  • Hide Izumi
    Dept. of Mol. & Pharmacol. Neurosci., Grad. Sch. of Biomed. & Health Sci., Hiroshima Univ.
  • Sakai Norio
    Dept. of Mol. & Pharmacol. Neurosci., Grad. Sch. of Biomed. & Health Sci., Hiroshima Univ.

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Other Title
  • Propofolとニコチンが誘発する細胞内カルシウム動態―細胞内小器官カルシウムインジケーターCEPIAを用いた観察

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<p>Propofol is known to cause vascular pain and hypotension as adverse effects. Prolonged use of propofol at high doses can produce fatal propofol infusion syndrome (PRIS). We have reported that propofol increased intracellular calcium ([Ca2+]i), which was accompanied by changes in the endoplasmic reticulum (ER) morphology, suggesting that the propofol-induced [Ca2+]i elevation was due to calcium leakage from the ER. We have also found that nicotine (>100 μM) elevates [Ca2+]i by a nicotinic receptor-independent mechanism, suggesting that nicotine mobilizes calcium from the ER to the cytoplasm.　In this study, we aimed to further elucidate the mechanism of propofol- and nicotine-induced [Ca2+]i elevation using the intracellular organelle calcium indicator CEPIA.</p><p>We used HeLa cells expressing CEPIAs and observed their fluorescence changes by fluorescence microscopy.</p><p>Propofol decreased the [Ca2+]i in the ER and simultaneously increased that in the cytosol in a concentration-dependent manner. The structural changes and the decrease in calcium concentration in the ER were synchronized. Thus, it was strongly suggested that propofol leaks calcium from the ER into the cytoplasm. In contrast, nicotine unexpectedly increased calcium concentrations at all sites in the cytosol, ER, and mitochondria. Nicotine may cause complex changes in calcium dynamics through extracellular, cytosolic, and intracellular organelles.</p><p>CEPIA has proven to be useful in elucidating drug-induced calcium kinetics by visualizing detailed calcium dynamics in intracellular organelles.</p>

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