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Calcium‐permeable presynaptic AMPA receptors in cerebellar molecular layer interneurones
Author(s) -
Rossi Bénédicte,
Maton Gilliane,
Collin Thibault
Publication year - 2008
Publication title -
the journal of physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.802
H-Index - 240
eISSN - 1469-7793
pISSN - 0022-3751
DOI - 10.1113/jphysiol.2008.159921
Subject(s) - ampa receptor , glutamate receptor , ryanodine receptor , biophysics , chemistry , ionotropic effect , voltage dependent calcium channel , neuroscience , nmda receptor , stimulation , long term depression , receptor , biology , calcium , biochemistry , organic chemistry
Axons of cerebellar molecular layer interneurones (MLIs) bear ionotropic glutamate receptors. Here, we show that these receptors elicit cytosolic [Ca 2+ ] transients in axonal varicosities following glutamate spillover induced by stimulation of parallel fibres (PFs). A spatial profile analysis indicates that these transients occur at the same locations when induced by PF stimulation or trains of action potentials. They are not affected by the NMDAR antagonist AP‐V, but are abolished by the AMPAR inhibitor GYKI‐53655. Mimicking glutamate spillover by a puff of AMPA triggers axonal [Ca 2+ ] i transients even in the presence of TTX. Addition of specific voltage‐dependent Ca 2+ channel (VDCC) blockers such as ω‐AGAIVA and ω‐conotoxin GVIA or broad range inhibitors such as Cd 2+ did not significantly inhibit the signal indicating the involvement of Ca 2+ ‐permeable AMPARs. This hypothesis is further supported by the finding that the subunit specific AMPAR antagonist IEM‐1460 blocks 75% of the signal. Bath application of AMPA increases the frequency and mean peak amplitude of GABAergic mIPSCs, an effect that is blocked by philanthotoxin‐433 (PhTx) and reinforced by facilitating concentrations of ryanodine. By contrast, a high concentration of ryanodine or dantrolene reduced the effects of AMPA on mIPSCs. Single‐cell RT‐PCR experiments show that all GluR1–4 subunits are potentially expressed in MLI. Taken together, the results suggest that Ca 2+ ‐permeable AMPARs are colocalized with VDCCs in axonal varicosities and can be activated by glutamate spillover through PF stimulation. The AMPAR‐mediated Ca 2+ signal is amplified by Ca 2+ ‐induced Ca 2+ release from intracellular stores, leading to GABA release by MLIs.