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

Maria Martire, R Luisi, E Panza, V Barrese, Fa Iannotti, D Viggiano, A Secondo, Lm Canzoniero, L Annunziato, M. Taglialatela

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24 Citazioni (Scopus)

Abstract

In this study, the functional consequences of the pharmacological modulation of the M-current (I(KM)) on cytoplasmic Ca(2+) intracellular Ca(2+)concentration ([Ca(2+)](i)) changes and excitatory neurotransmitter release triggered by various stimuli from isolated rat cortical synaptosomes have been investigated. K(v)7.2 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 I(KM) activator retigabine (RT, 10 microM) inhibited [(3)H]D-aspartate ([(3)H]D-Asp) release and caused membrane hyperpolarization; both these effects were prevented by the I(KM) blocker XE-991 (20 microM). The I(KM) activators RT (0.1-30 microM), flupirtine (10 microM) and BMS-204352 (10 microM) inhibited 20 mM [K(+)](e)-induced synaptosomal [Ca(2+)](i) increases; XE-991 (20 microM) abolished RT-induced inhibition of depolarization-triggered [Ca(2+)](i) transients. The P/Q-type voltage-sensitive Ca(2+)channel (VSCC) blocker omega-agatoxin IVA prevented RT-induced inhibition of depolarization-induced [Ca(2+)](i) increase and [(3)H]D-Asp release, whereas the N-type blocker omega-conotoxin GVIA failed to do so. Finally, 10 microM RT did not modify the increase of [Ca(2+)](i) and the resulting enhancement of [(3)H]D-Asp release induced by [Ca(2+)](i) mobilization from intracellular stores, or by store-operated Ca(2+)channel activation. Collectively, the present data reveal that the pharmacological activation of I(KM) regulates depolarization-induced [(3)H]D-Asp release from cerebrocortical synaptosomes by selectively controlling the changes of [Ca(2+)](i) occurring through P/Q-type VSCCs.
Lingua originaleEnglish
pagine (da-a)168-181
Numero di pagine14
RivistaJournal of Neurochemistry
Volume109
DOI
Stato di pubblicazionePubblicato - 2009

Keywords

  • Ca2+ channels
  • D-aspartate release
  • K+ channels

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