Inhibition of voltage-gated calcium channels by fluoxetine in rat hippocampal pyramidal cells

Ferenc Deák, Bálint Lasztóczi, Pál Pacher, Gábor L. Petheö, Kecskeméti Valéria Kecskeméti, András Spät

Research output: Contribution to journalArticle

102 Scopus citations

Abstract

Fluoxetine, an antidepressant which is used world-wide, is a prominent member of the class of selective serotonin re-uptake inhibitors. Recently, inhibition of voltage-gated Na+ and K+ channels by fluoxetine has also been reported. We examined the effect of fluoxetine on voltage-gated calcium channels using the patch-clamp technique in the whole-cell configuration. In hippocampal pyramidal cells, fluoxetine inhibited the low-voltage-activated (T-type) calcium current with an IC50 of 6.8 μM. Fluoxetine decreased the high-voltage-activated (HVA) calcium current with an IC50 between 1 and 2 μM. Nifedipine and ω-conotoxin GVIA inhibited the HVA current by 24% and 43%, respectively. Fluoxetine (3 μM), applied in addition to nifedipine or ω-conotoxin, further reduced the current. When fluoxetine (3 μM) was applied first neither nifedipine nor ω-conotoxin attenuated the remaining component of the HVA current. This observation indicates that fluoxetine inhibits both L- and N-type currents. In addition, fluoxetine inhibited the HVA calcium current in carotid body type I chemoreceptor cells and pyramidal neurons prepared from prefrontal cortex. In hippocampal pyramidal cells high K+-induced seizure-like activity was inhibited by 1 μM fluoxetine; the mean burst duration was shortened by an average of 44%. These results provide evidence for inhibition of T-, N- and L-type voltage-gated calcium channels by fluoxetine at therapeutically relevant concentrations. (C) 2000 Elsevier Science Ltd.

Original languageEnglish (US)
Pages (from-to)1029-1036
Number of pages8
JournalNeuropharmacology
Volume39
Issue number6
DOIs
StatePublished - May 1 2000
Externally publishedYes

Keywords

  • Depression
  • Epilepsy
  • Fluoxetine
  • Hippocampus
  • Pyramidal neuron
  • Voltage-gated calcium channel

ASJC Scopus subject areas

  • Pharmacology
  • Cellular and Molecular Neuroscience

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    Deák, F., Lasztóczi, B., Pacher, P., Petheö, G. L., Valéria Kecskeméti, K., & Spät, A. (2000). Inhibition of voltage-gated calcium channels by fluoxetine in rat hippocampal pyramidal cells. Neuropharmacology, 39(6), 1029-1036. https://doi.org/10.1016/S0028-3908(99)00206-3