Evoked GABA release is not mediated by N-type VDCC in the frontal cortex of awake rats: effects of neomycin
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J M Martínez-Martos1, M C Iribar, J M Peinado
1Department of Biochemistry, F. Oloriz Institute of Neurosciences, School of Medicine, University of Granada, Spain.
Abstract:
The purpose of the present study was to analyze the Ca2+ channel involved in GABA release under resting and K(+)-evoked conditions in vivo. We used microdialysis to investigate the effects of the voltage-dependent calcium channel (VDCC) blockers neomycin, kanamycin, and omega-conotoxin GVIA, and the voltage-dependent Na+ channel blocker tetrodotoxin, in the frontal cortex of awake rats. The GABA content in frontal dialysates was analyzed by high performance liquid chromatography coupled to fluorescence detection. Basal GABA release was kanamycin, omega-conotoxin, and tetrodotoxin resistant, whereas neomycin induced a significant increase from the basal level. The K(+)-evoked release of GABA was kanamycin and omega-conotoxin resistant, but tetrodotoxin sensitive. The effects of neomycin were masked by the action of this drug on basal release. These results suggest that neomycin may affect GABA release in the frontal cortex through a mechanism independent of VDCC. In addition, the K(+)-evoked release of GABA in this cortical area was not mediated by the N-type voltage-dependent calcium channels, but was dependent on neural activity or TTX sensitive.
Insights
Neomycin increases basal GABA release in rat frontal cortex, independent of calcium channels. Potassium-evoked GABA release relies on neural activity, not N-type calcium channels.
Area of Science:
- Neuroscience
- Neuropharmacology
Background:
- Gamma-aminobutyric acid (GABA) is the primary inhibitory neurotransmitter in the central nervous system.
- Understanding the regulation of GABA release is crucial for comprehending neuronal function and dysfunction.
Purpose of the Study:
- To investigate the role of calcium channels in GABA release in the rat frontal cortex under resting and stimulated conditions.
- To differentiate the mechanisms of basal and evoked GABA release.
Main Methods:
- In vivo microdialysis in awake rats.
- Administration of voltage-dependent calcium channel (VDCC) blockers (neomycin, kanamycin, omega-conotoxin GVIA) and a sodium channel blocker (tetrodotoxin).
- High-performance liquid chromatography with fluorescence detection to quantify GABA levels in dialysates.
Main Results:
- Basal GABA release was resistant to kanamycin, omega-conotoxin, and tetrodotoxin, but neomycin significantly increased it.
- Potassium-evoked GABA release was resistant to kanamycin and omega-conotoxin but sensitive to tetrodotoxin.
- Neomycin's effect on basal release masked its potential role in evoked release.
Conclusions:
- Neomycin may influence frontal cortex GABA release via a non-VDCC-dependent pathway.
- Potassium-evoked GABA release in this region is not mediated by N-type VDCCs but depends on neural activity or tetrodotoxin-sensitive mechanisms.