Ca2+ entry via AMPA-type glutamate receptors triggers Ca2+-induced Ca2+ release from ryanodine receptors in rat spiral ganglion neurons.

Abstract Ryanodine receptor (RyR)-gated Ca 2+ stores have recently been identified in cochlear spiral ganglion neurons (SGN) and likely contribute to Ca 2+ signalling associated with auditory neurotransmission. Here, we identify an ionotropic glutamate receptor signal transduction pathway which invokes RyR-gated Ca 2+ stores in SGN via Ca 2+ -induced Ca 2+ release (CICR). Ca 2+ levels were recorded in SGN in situ within rat cochlear slices (postnatal day 0–17) using the Ca 2+ indicator fluo-4. RyR-gated Ca 2+ stores were confirmed by caffeine-induced increases in intracellular Ca 2+ which were blocked by ryanodine (100 μM) and were independent of external Ca 2+ . Glutamate evoked comparable increases in intracellular Ca 2+ , but required the presence of external Ca 2+ . Ca 2+ influx via the glutamate receptor was found to elicit CICR via RyR-gated Ca 2+ stores, as shown by the inhibition of the response by prior depletion of the Ca 2+ stores with caffeine, the SERCA inhibitor thapsigargin, or ryanodine. The glutamate analogue AMPA (α-Amino-3-hydroxy-5-methylisoxazole-4-propionic acid) elicited Ca 2+ responses that could be inhibited by caffeine. Glutamate- and AMPA-mediated Ca 2+ responses were eliminated with the AMPA/Kainate receptor antagonist DNQX (6,7-dinitroquinoxaline-2,3-dione). These data demonstrate functional coupling between somatic AMPA-type glutamate receptors and intracellular Ca 2+ stores via RyR-dependent CICR in primary auditory neurons.