title: Pre-synaptic BK channels selectively control glutamate versus GABA release from cortical and hippocampal nerve terminals.
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.
authors.affiliation: Institute of Pharmacology, Catholic University of Sacred Heart, Rome, Italy.
authors.forename: Maria
authors.initials: M
authors.lastname: Martire
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Barrese
authors.forename: Monia
authors.initials: M
authors.lastname: D'Amico
authors.forename: Fabio Arturo
authors.initials: FA
authors.lastname: Iannotti
authors.forename: Rocco
authors.initials: R
authors.lastname: Pizzarelli
authors.forename: Irene
authors.initials: I
authors.lastname: Samengo
authors.forename: Davide
authors.initials: D
authors.lastname: Viggiano
authors.forename: Peter
authors.initials: P
authors.lastname: Ruth
authors.forename: Enrico
authors.initials: E
authors.lastname: Cherubini
authors.forename: Maurizio
authors.initials: M
authors.lastname: Taglialatela
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D019540:Area Under Curve; D001224:Aspartic Acid / Q000378:metabolism; D002118:Calcium / Q000378:metabolism; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology*; D006224:Cricetinae; D003412:Cricetulus; D004298:Dopamine / Q000378:metabolism; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects; D005786:Gene Expression Regulation / Q000187:drug effects; D018698:Glutamic Acid / Q000378:metabolism*; D006624:Hippocampus / Q000166:cytology*; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D018613:Microscopy, Confocal; D009638:Norepinephrine / Q000378:metabolism; D010455:Peptides / Q000494:pharmacology; D024681:Potassium Channels, Calcium-Activated / Q000172:deficiency / Q000378:metabolism*; D017729:Presynaptic Terminals / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D016708:Synaptophysin / Q000378:metabolism; D013574:Synaptosomes / Q000378:metabolism; D014162:Transfection / Q000379:methods; D014316:Tritium / Q000378:metabolism; D050598:Vesicular Glutamate Transport Protein 1 / Q000378:metabolism; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
chemical_list: D010455:Peptides; D024681:Potassium Channels, Calcium-Activated; C493465:Slc17a7 protein, mouse; D016708:Synaptophysin; D050598:Vesicular Glutamate Transport Protein 1; D014316:Tritium; D001224:Aspartic Acid; D018698:Glutamic Acid; D005680:gamma-Aminobutyric Acid; C064719:iberiotoxin; D002118:Calcium; D004298:Dopamine; D009638:Norepinephrine