Activation of pre-synaptic M-type K+ channels inhibits [ 3H]d-aspartate release by reducing Ca2+ entry through P/Q-type voltage-gated Ca2+channels

Rosa Luisi, Elisabetta Panza, Vincenzo Barrese, Fabio Arturo Iannotti, Davide Viggiano, Agnese Secondo, Lorella Maria Teresa Canzoniero, Maria Martire, Lucio Annunziato, Maurizio Taglialatela

Research output: Contribution to journalArticle

Abstract

In this study, the functional consequences of the pharmacological modulation of the M-current (IKM) on cytoplasmic Ca2+ intracellular Ca2+concentration ([Ca2+]i) changes and excitatory neurotransmitter release triggered by various stimuli from isolated rat cortical synaptosomes have been investigated. Kv7.2 immunoreactivity was identified in pre-synaptic elements in cortical slices and isolated glutamatergic cortical synaptosomes. In cerebrocortical synaptosomes exposed to 20 mM [K+]e, the IKM activator retigabine (RT, 10 μM) inhibited [3H]d-aspartate ([ 3H]d-Asp) release and caused membrane hyperpolarization; both these effects were prevented by the IKM blocker XE-991 (20 μM). The IKM activators RT (0.1-30 μM), flupirtine (10 μM) and BMS-204352 (10 μM) inhibited 20 mM [K+]e-induced synaptosomal [Ca2+]i increases; XE-991 (20 μM) abolished RT-induced inhibition of depolarization-triggered [Ca 2+]i transients. The P/Q-type voltage-sensitive Ca 2+channel (VSCC) blocker ω-agatoxin IVA prevented RT-induced inhibition of depolarization-induced [Ca2+]i increase and [3H]d-Asp release, whereas the N-type blocker ω-conotoxin GVIA failed to do so. Finally, 10 μM RT did not modify the increase of [Ca 2+]i and the resulting enhancement of [3H]d-Asp release induced by [Ca2+]i mobilization from intracellular stores, or by store-operated Ca2+channel activation. Collectively, the present data reveal that the pharmacological activation of IKM regulates depolarization-induced [3H]d-Asp release from cerebrocortical synaptosomes by selectively controlling the changes of [Ca2+]i occurring through P/Q-type VSCCs.

Original languageEnglish
Pages (from-to)168-181
Number of pages14
JournalJournal of Neurochemistry
Volume109
Issue number1
DOIs
Publication statusPublished - Apr 2009

Keywords

  • Excitatory amino acid release
  • Intracellular Ca
  • K 7.2 subunits
  • M-current
  • Retigabine
  • Synaptosomes

ASJC Scopus subject areas

  • Biochemistry
  • Cellular and Molecular Neuroscience

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    Luisi, R., Panza, E., Barrese, V., Iannotti, F. A., Viggiano, D., Secondo, A., Canzoniero, L. M. T., Martire, M., Annunziato, L., & Taglialatela, M. (2009). Activation of pre-synaptic M-type K+ channels inhibits [ 3H]d-aspartate release by reducing Ca2+ entry through P/Q-type voltage-gated Ca2+channels. Journal of Neurochemistry, 109(1), 168-181. https://doi.org/10.1111/j.1471-4159.2009.05945.x