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

Research output: Contribution to journalArticle

24 Citations (Scopus)

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

Fingerprint

Fluoxetine
PC12 Cells
Adenosine Triphosphate
Inositol Phosphates
Nimodipine
Calcium Signaling
Fura-2
Ion Channels
Constriction
Antidepressive Agents
Inhibitory Concentration 50
Calcium

All Science Journal Classification (ASJC) codes

  • Pharmacology
  • Cellular and Molecular Neuroscience

Cite this

Kim, Hee Jung ; Choi, Jin Sung ; Lee, Yeo Min ; Shim, Eun Young ; Hong, Sun Hwa ; Kim, Myung Jun ; Min, Do Sik ; Rhie, Duck Joo ; Kim, Myung Suk ; Jo, Yang Hyeok ; Hahn, Sang June ; Yoon, Shin Hee. / Fluoxetine inhibits ATP-induced [Ca2+]i increase in PC12 cells by inhibiting both extracellular Ca2+ influx and Ca 2+ release from intracellular stores. In: Neuropharmacology. 2005 ; Vol. 49, No. 2. pp. 265-274.
@article{5bf23ece03404964b4244f57ce06a5fe,
title = "Fluoxetine inhibits ATP-induced [Ca2+]i increase in PC12 cells by inhibiting both extracellular Ca2+ influx and Ca 2+ release from intracellular stores",
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.",
author = "Kim, {Hee Jung} and Choi, {Jin Sung} and Lee, {Yeo Min} and Shim, {Eun Young} and Hong, {Sun Hwa} and Kim, {Myung Jun} and Min, {Do Sik} and Rhie, {Duck Joo} and Kim, {Myung Suk} and Jo, {Yang Hyeok} and Hahn, {Sang June} and Yoon, {Shin Hee}",
year = "2005",
month = "8",
day = "1",
doi = "10.1016/j.neuropharm.2005.03.007",
language = "English",
volume = "49",
pages = "265--274",
journal = "Neuropharmacology",
issn = "0028-3908",
publisher = "Elsevier Limited",
number = "2",

}

Fluoxetine inhibits ATP-induced [Ca2+]i increase in PC12 cells by inhibiting both extracellular Ca2+ influx and Ca 2+ release from intracellular stores. / Kim, Hee Jung; Choi, Jin Sung; Lee, Yeo Min; Shim, Eun Young; Hong, Sun Hwa; Kim, Myung Jun; Min, Do Sik; Rhie, Duck Joo; Kim, Myung Suk; Jo, Yang Hyeok; Hahn, Sang June; Yoon, Shin Hee.

In: Neuropharmacology, Vol. 49, No. 2, 01.08.2005, p. 265-274.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Fluoxetine inhibits ATP-induced [Ca2+]i increase in PC12 cells by inhibiting both extracellular Ca2+ influx and Ca 2+ release from intracellular stores

AU - Kim, Hee Jung

AU - Choi, Jin Sung

AU - Lee, Yeo Min

AU - Shim, Eun Young

AU - Hong, Sun Hwa

AU - Kim, Myung Jun

AU - Min, Do Sik

AU - Rhie, Duck Joo

AU - Kim, Myung Suk

AU - Jo, Yang Hyeok

AU - Hahn, Sang June

AU - Yoon, Shin Hee

PY - 2005/8/1

Y1 - 2005/8/1

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=21644482673&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=21644482673&partnerID=8YFLogxK

U2 - 10.1016/j.neuropharm.2005.03.007

DO - 10.1016/j.neuropharm.2005.03.007

M3 - Article

C2 - 15993448

AN - SCOPUS:21644482673

VL - 49

SP - 265

EP - 274

JO - Neuropharmacology

JF - Neuropharmacology

SN - 0028-3908

IS - 2

ER -