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GABA induces norepinephrine exocytosis from hippocampal noradrenergic axon terminals by a dual mechanism involving different voltage‐sensitive calcium channels
Author(s) -
Fassio Anna,
Rossi Federico,
Bonanno Giambattista,
Raiteri Maurizio
Publication year - 1999
Publication title -
journal of neuroscience research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.72
H-Index - 160
eISSN - 1097-4547
pISSN - 0360-4012
DOI - 10.1002/(sici)1097-4547(19990801)57:3<324::aid-jnr4>3.0.co;2-z
Subject(s) - gabaa receptor , bicuculline , chemistry , voltage dependent calcium channel , exocytosis , gamma aminobutyric acid , receptor , biophysics , medicine , endocrinology , pharmacology , calcium , biology , biochemistry , organic chemistry , secretion
GABA can evoke norepinephrine (NE) release by activating GABA A receptors or GABA transporters on noradrenergic terminals. The heterocarrier‐induced release occurs by conventional exocytosis. We here characterized the mechanism of the GABA A receptor‐induced release and investigated what type(s) of voltage‐sensitive Ca 2+ channels (VSCCs) are involved in the GABA heterocarrier and GABA A receptor‐evoked release. The effect of GABA in superfused rat hippocampal synaptosomes prelabeled with [ 3 H]‐NE was partially prevented by bicuculline or the GABA uptake inhibitor SKF 89976A and abolished by blocking both GABA A receptors and GABA transporters. The release elicited through GABA A receptors was Ca 2+ ‐dependent, prevented by Cd 2+ or by botulinum toxin C, and modulated through α 2 autoreceptors. The GABA A receptor‐evoked release was insensitive to nifedipine and to ω‐conotoxin MVIIC, but was inhibited (∼50%) by ω‐conotoxin GVIA. The heterocarrier‐evoked release, nifedipine‐insensitive, was inhibited ∼30% either by ω‐conotoxin GVIA or by ω‐conotoxin MVIIC; the combined toxins produced ∼60% inhibition. To conclude: a) the releases of NE evoked by activation of GABA A receptors and GABA heterocarriers are additive, although they both occur by conventional exocytosis; b) the heterocarrier‐induced release requires activation of N and P/Q type channels, whereas the GABA A receptor‐induced release only involves channels of the N type. J. Neurosci. Res. 57:324–331, 1999. © 1999 Wiley‐Liss, Inc.