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

Abstract

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.