Calcium influx through N-methyl-D-aspartate receptors triggers GABA release at interneuron-Purkinje cell synapse in rat cerebellum.

Journal article

Ca(2+)-dependent neurotransmitter release was originally thought to occur only following activation of presynaptic voltage-gated calcium channels after a presynaptic action potential. Recent evidence suggests that not only opening of voltage-gated but also ligand-gated ion channels, such as neurotransmitter receptors, can trigger exocytosis, as well as Ca(2+) release from intracellular Ca(2+) stores. It was shown that activation of N-methyl-d-aspartate (NMDA) receptors on presynaptic interneurons led to increases in GABA release from these neurons onto postsynaptic Purkinje cells in rat cerebellum in the presence of tetrodotoxin (TTX), suggesting a presynaptic location for the underlying NMDA receptors. However, the mechanism for the NMDA-induced increase in GABA release remained unclear. The present study addresses the question whether Ca(2+) influx through presynaptic NMDA receptors alone is sufficient to trigger presynaptic GABA release at this synapse or whether activation of presynaptic NMDA receptors leads to opening of voltage-gated Ca(2+) channels, thereby increasing exocytosis. The results suggest that the NMDA-induced increase in presynaptic GABA release neither requires activation of presynaptic voltage-gated Ca(2+) channels nor Ca(2+) release from presynaptic Ca(2+) stores. It is concluded that Ca(2+) influx through the NMDA receptor alone is sufficient to drive presynaptic GABA release at the rat interneuron-Purkinje cell synapse.

Authors: Glitsch, M

• Publication status: Published
• Journal: Neuroscience
• Volume: 151
• Issue: 2
• Pages: 403-409
• Publication date: 2008-01-01
• DOI: 10.1016/j.neuroscience.2007.10.024
• EISSN: 1873-7544
• ISSN: 0306-4522
• Language: English
• Keywords: Calcium; Animals; N-Methylaspartate; Synapses; Rats; Excitatory Amino Acid Agonists; Calcium Channels; Purkinje Cells; Calcium Signaling; Receptors, Presynaptic; gamma-Aminobutyric Acid; Cadmium; Patch-Clamp Techniques; Calcium Channel Blockers; Receptors, N-Methyl-D-Aspartate; Cerebellum; Rats, Sprague-Dawley; Electrophysiology; Interneurons