Korean J Physiol Pharmacol.  2004 Feb;8(1):57-63.

Efffects of Fluoxetine on ATP-induced Calcium Signaling in PC12 Cells

• Lee YM
• Kim HJ
• Hong SH
• Kim MJ
• Min DS
• Rhie DJ
• Kim MS
• Jo YH
• Hahn SJ
• Yoon SH

Abstract

Fluoxetine, a widely used anti-depressant compound, has several additional effects, including blockade of voltage-gated ion channels. We examined whether fluoxetine affects ATP-induced calcium signaling in PC12 cells by using fura-2-based digital calcium imaging and assay for [3H]-inositol phosphates (IPs). Treatment with ATP (100microM) for 2 min induced [Ca2+]i increases. The ATP-induced [Ca2+]i increases were significantly decreased by removal of extracellular Ca2+ and treatment with the inhibitor of endoplasmic reticulum Ca2+ ATPase thapsigargin (1microM). Treatment with fluoxetine for 5 min blocked the ATP-induced [Ca2+]i increase concentration-dependently. Treatment with fluoxetine (30microM) for 5 min blocked the ATP-induced [Ca2+]i increase following removal of extracellular Ca2+ and depletion of intracellular Ca2+ stores. While treatment with the L-type Ca2+ channel antagonist nimodipine for 10 min inhibited the ATP-induced [Ca2+]i increases significantly, treatment with fluoxetine alone blocked the ATP-induced responses. Treatment with fluoxetine also inhibited the 50 mM K+-induced [Ca2+]i increases completely. However, treatment with fluoxetine did not inhibit the ATP-induced [3H]-IPs formation. Collectively, we conclude that fluoxetine inhibits ATP-induced [Ca2+]i increases in PC12 cells by inhibiting both an influx of extracellular Ca2+ and a release of Ca2+ from intracellular stores without affecting IPs formation.

Keyword

ATP; Fluoxetine; Inositol phosphates; Non-selective cation channels; PC12 cells; Voltage- gated Ca2+ channels

MeSH Terms

Adenosine Triphosphate
Animals
Calcium Signaling*
Calcium*
Calcium-Transporting ATPases
Endoplasmic Reticulum
Fluoxetine*
Inositol Phosphates
Ion Channels
Nimodipine
PC12 Cells*
Phosphates
Thapsigargin
Adenosine Triphosphate
Calcium
Calcium-Transporting ATPases
Fluoxetine
Inositol Phosphates
Ion Channels
Nimodipine
Phosphates
Thapsigargin