Effects of voltage-sensitive calcium channel blockers on extracellular dopamine levels in rat striatum

Amina El Ayadi, Ihssan Afailal, Mohammed Errami

Research output: Contribution to journalArticlepeer-review

10 Scopus citations

Abstract

Various subtypes of voltage-sensitive calcium channels (VSCCs) support the release of dopamine (DA) in the central nervous system. Using in vivo microdialysis, we investigate the influence of these subtypes of calcium channels on dopaminergic terminals in the rat striatum. L-type (nifedipine-sensitive), N-type (ω-conotoxin GVIA-sensitive), or N- and P/Q-type (ω-conotoxin MVIIC-sensitive) Ca2+ channels were blocked using selective antagonists injected locally, and K+-evoked DA release was measured in freely moving animals. K+(100 mM) induced a massive increase of basal DA extracellular levels (930%) and was without significant effect on extracellular levels of DA metabolites DOPAC and HVA, and on the serotonin metabolite 5HIAA. ω-Conotoxin GVIA (1 μM) and ω-conotoxin MVIIC (1 μM) significantly reduced the K+-evoked DA release by 55 and 62%, respectively. The simultaneous application of the two conotoxins at the same concentration reduced K+-evoked DA release by 66%. Nifedipine (10 μM) had no significant effect on K+-evoked DA release, while neomycin, a nonspecific VSCC blocker, produced a highly significant decrease when applied at 250 and 500 μM (56 and 75%, respectively). The compounds, however, had no effect on basal DA release and on the levels of extracellular DOPAC, HVA, and 5HIAA. These results suggest that under high and persistent conditions of membrane depolarization (15 min, 100 mM K+), striatal DA release is mainly mediated by N-type VSCCs.

Original languageEnglish (US)
Pages (from-to)121-131
Number of pages11
JournalMetabolic brain disease
Volume16
Issue number3-4
DOIs
StatePublished - 2001
Externally publishedYes

Keywords

  • Calcium channels
  • Dopamine
  • Microdialysis
  • Neomycin
  • Nifedipine
  • ω-conotoxin GVIA
  • ω-conotoxin MVIIC

ASJC Scopus subject areas

  • Biochemistry
  • Clinical Neurology
  • Cellular and Molecular Neuroscience

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