Presynaptic BK channels selectively control glutamate versus GABA release from cortical and hippocampal nerve terminals.

Maria Martire, Monia D'Amico, Irene Angela Samengo, V. Barrese, F. Iannotti, R. Pizzarelli, D. Viaggiano, P. Ruth, E. Cherubini, M. Taglialatela

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34 Citazioni (Scopus)

Abstract

In the present study, by means of genetic, biochemical, morphological, and electrophysiological approaches, the role of large-conductance voltage- and Ca(2+)-dependent K(+) channels (BK channels) in the release of excitatory and non-excitatory neurotransmitters at hippocampal and non-hippocampal sites has been investigated. The results obtained show that the pharmacological modulation of pre-synaptic BK channels selectively regulates [(3)H]D-aspartate release from cortical and hippocampal rat synaptosomes, but it fails to influence the release of excitatory neurotransmitters from cerebellar nerve endings or that of [(3)H]GABA, [(3)H]Noradrenaline, or [(3)H]Dopamine from any of the brain regions investigated. Confocal immunofluorescence experiments in hippocampal or cerebrocortical nerve terminals revealed that the main pore-forming BK α subunit was more abundantly expressed in glutamatergic (vGLUT1(+)) versus GABAergic (GAD(65-67)(+)) nerve terminals. Double patch recordings in monosynaptically connected hippocampal neurons in culture confirmed a preferential control exerted by BK channels on glutamate over GABA release. Altogether, the present results highlight a high degree of specificity in the regulation of the release of various neurotransmitters from distinct brain regions by BK channels, supporting the concept that BK channel modulators can be used to selectively limit excessive excitatory amino acid release, a major pathogenetic mechanism in several neuropsychiatric disorders.
Lingua originaleEnglish
pagine (da-a)411-422
Numero di pagine12
RivistaJournal of Neurochemistry
Volume115
DOI
Stato di pubblicazionePubblicato - 2010

Keywords

  • BK channels
  • excitotoxicity
  • glutamate release
  • iberiotoxin
  • paxilline
  • synaptosomes

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