Involvement of KCNQ2 subunits in [3H]dopamine release triggered by depolarization and pre-synaptic muscarinic receptor activation from rat striatal synaptosomes

Maria Martire, Monia D'Amico, Elisabetta Panza, Francesco Miceli, Davide Viggiano, Francesco Lavergata, Fabio Arturo Iannotti, Vincenzo Barrese, Paolo Preziosi, Lucio Annunziato, Maurizio Taglialatela

Research output: Contribution to journalArticlepeer-review

Abstract

KCNQ2 and KCNQ3 subunits encode for the muscarinic-regulated current (IKM), a sub-threshold voltage-dependent K+ current regulating neuronal excitability. In this study, we have investigated the involvement of IKM in dopamine (DA) release from rat striatal synaptosomes evoked by elevated extracellular K+ concentrations ([K+]e) and by muscarinic receptor activation. [ 3H]dopamine ([3H]DA) release triggered by 9 mmol/L [K +]e was inhibited by the IKM activator retigabine (0.01-30 μmol/L; Emax = 54.80 ± 3.85%; IC 50 = 0.50 ± 0.36 μmol/L). The IKM blockers tetraethylammonium (0.1-3 mmol/L) and XE-991 (0.1-30 μmol/L) enhanced K +-evoked [3H]DA release and prevented retigabine-induced inhibition of depolarization-evoked [3H]DA release. Retigabine-induced inhibition of K+-evoked [3H]DA release was also abolished by synaptosomal entrapment of blocking anti-KCNQ2 polyclonal antibodies, an effect prevented by antibody pre-absorption with the KCNQ2 immunizing peptide. Furthermore, the cholinergic agonist oxotremorine (OXO) (1-300 μmol/L) potentiated 9 mmol/L [K+]e-evoked [ 3H]DA release (Emax = 155 ± 9.50%; EC50 = 25 ± 1.80 μmol/L). OXO (100 μmol/L)-induced [3H]DA release enhancement was competitively inhibited by pirenzepine (1-10 nmol/L) and abolished by the M3-preferring antagonist 4-diphenylacetoxy N-methylpiperidine methiodide (1 μmol/L), but was unaffected by the M 1-selective antagonist MT-7 (10-100 nmol/L) or by Pertussis toxin (1.5-3 μg/mL), which uncouples M2- and M4-mediated responses. Finally, OXO-induced potentiation of depolarization-induced [ 3H]DA release was not additive to that produced by XE-991 (10 μmol/L), was unaffected by retigabine (10 μmol/L), and was abolished by synaptosomal entrapment of anti-KCNQ2 antibodies. Collectively, these findings indicate that, in rat striatal nerve endings, IKM channels containing KCNQ2 subunits regulate depolarization-induced DA release and that I KM suppression is involved in the reinforcement of depolarization-induced DA release triggered by the activation of pre-synaptic muscarinic heteroreceptors.

Original languageEnglish
Pages (from-to)179-193
Number of pages15
JournalJournal of Neurochemistry
Volume102
Issue number1
DOIs
Publication statusPublished - Jul 2007

Keywords

  • Dopamine release
  • KCNQ2 subunits
  • Modulation
  • Muscarinic
  • Potassium channels
  • Retigabine
  • Striatum

ASJC Scopus subject areas

  • Biochemistry
  • Cellular and Molecular Neuroscience

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