CB1 receptors diminish both Ca(2+) influx and glutamate release through two different mechanisms active in distinct populations of cerebrocortical nerve terminals
| Autor: | José Sánchez-Prieto, Magdalena Torres, María del Carmen Godino |
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| Rok vydání: | 2007 |
| Předmět: |
Male
Cannabinoid receptor Morpholines Presynaptic Terminals Glutamic Acid Stimulation Tetrodotoxin Naphthalenes Biochemistry Potassium Chloride Cellular and Molecular Neuroscience chemistry.chemical_compound Receptor Cannabinoid CB1 Animals Rats Wistar Cerebral Cortex Tetraethylammonium Glutamate receptor Depolarization Benzoxazines Rats chemistry Metabotropic glutamate receptor Biophysics Ligand-gated ion channel Calcium Calcium Channels Neuroscience Synaptosomes |
| Zdroj: | Journal of neurochemistry. 101(6) |
| ISSN: | 0022-3042 |
| Popis: | We have investigated the mechanisms by which activation of cannabinoid receptors reduces glutamate release from cerebrocortical nerve terminals. Glutamate release evoked by depolarization of nerve terminals with high KCl (30 mmol/L) involves N and P/Q type Ca(2+)channel activation. However, this release of glutamate is independent of Na(+) or K(+) channel activation as it was unaffected by blockers of these channels (tetrodotoxin -TTX- or tetraethylammonium TEA). Under these conditions in which only Ca(2+) channels contribute to pre-synaptic activity, the activation of cannabinoid receptors with WIN55,212-2 moderately reduced glutamate release (26.4 +/- 1.2%) by a mechanism that in this in vitro model is resistant to TTX and consistent with the inhibition of Ca(2+) channels. However, when nerve terminals are stimulated with low KCl concentrations (5-10 mmol/L) glutamate release is affected by both Ca(2+) antagonists and also by TTX and TEA, indicating the participation of Na(+) and K(+) channel firing in addition to Ca(2+) channel activation. Interestingly, stimulation of nerve terminals with low KCl concentrations uncovered a mechanism that further inhibited glutamate release (81.78 +/- 4.9%) and that was fully reversed by TEA. This additional mechanism is TTX-sensitive and consistent with the activation of K(+) channels. Furthermore, Ca(2+) imaging of single boutons demonstrated that the two pre-synaptic mechanisms by which cannabinoid receptors reduce glutamate release operate in distinct populations of nerve terminals. |
| Databáze: | OpenAIRE |
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