Fluoxetine inhibits ATP-induced [Ca2+]i increase in PC12 cells by inhibiting both extracellular Ca2+ influx and Ca 2+ release from intracellular stores

Hee Jung Kim, Jin Sung Choi, Yeo Min Lee, Eun Young Shim, Sun Hwa Hong, Myung Jun Kim, Do Sik Min, Duck Joo Rhie, Myung Suk Kim, Yang Hyeok Jo, Sang June Hahn, Shin Hee Yoon

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Abstract

Fluoxetine, a widely used antidepressant, has additional effects, including the blocking of voltage-gated ion channels. We examined whether fluoxetine affects ATP-induced calcium signaling in PC12 cells using fura-2-based digital calcium imaging, an assay for [3H]-inositol phosphates (IPs) and whole-cell patch clamping. Treatment with ATP (100 μM) for 2 min induced increases in intracellular free Ca2+ concentrations ([Ca 2+]i). Treatment with fluoxetine (100 nM to 30 μM) for 5 min inhibited the ATP-induced [Ca2+]i increases in a concentration-dependent manner (IC50 = 1.85 μM). Treatment with fluoxetine (1.85 μM) for 5 min significantly inhibited the ATP-induced responses following the removal of extracellular Ca2+ or depletion of intracellular Ca2+ stores. Whereas treatment for 10 min with nimodipine (1 μM) significantly inhibited the ATP-induced [Ca 2+]i increase, treatment with fluoxetine further inhibited the ATP-induced response. Treatment with fluoxetine significantly inhibited [Ca2+]i increases induced by 50 mM K+. In addition, treatment with fluoxetine markedly inhibited ATP-induced inward currents in a concentration-dependent manner. However, treatment with fluoxetine did not inhibit ATP-induced [3H]-IPs formation. Therefore, we conclude that fluoxetine inhibits ATP-induced [Ca2+]i increases in PC12 cells by inhibiting both the influx of extracellular Ca 2+ and the release of Ca2+ from intracellular stores without affecting IPs formation.

Original languageEnglish
Pages (from-to)265-274
Number of pages10
JournalNeuropharmacology
Volume49
Issue number2
DOIs
Publication statusPublished - 2005 Aug 1

All Science Journal Classification (ASJC) codes

  • Pharmacology
  • Cellular and Molecular Neuroscience

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    Kim, H. J., Choi, J. S., Lee, Y. M., Shim, E. Y., Hong, S. H., Kim, M. J., Min, D. S., Rhie, D. J., Kim, M. S., Jo, Y. H., Hahn, S. J., & Yoon, S. H. (2005). Fluoxetine inhibits ATP-induced [Ca2+]i increase in PC12 cells by inhibiting both extracellular Ca2+ influx and Ca 2+ release from intracellular stores. Neuropharmacology, 49(2), 265-274. https://doi.org/10.1016/j.neuropharm.2005.03.007