Elevation of intradendritic sodium concentration mediated by synaptic activation of metabotropic glutamate receptors in cerebellar Purkinje cells

Cerebellar Purkinje cells express both ionotropic glutamate receptors and metabotropic glutamate receptors. Brief tetanic stimulation of parallel fibers in rat and mouse cerebellar slices evokes a slow excitatory postsynaptic current in Purkinje cells that is mediated by the mGluR₁ subtype of metabotropic glutamate receptors. The effector system underlying this mGluR₁ EPSC has not yet been identified. In the present study, we recorded the mGluR1 EPSC using the whole-cell patch-clamp technique in combination with microfluorometric recordings of the intracellular sodium concentration ([Na⁺](i)) by means of the fluorescent sodium indicator SBFI. The mGluR₁ EPSC was induced by local parallel fibre stimulation in the presence of the ionotropic glutamate receptor antagonists NBQX and D-APV and the GABA(A) receptor antagonists bicuculline or picrotoxin, The mGluR1 EPSC was associated with an increase in [Na⁺](i) that was restricted to a specific portion of the dendritic tree. The mGluR₁ EPSC as well as the increase in [Na⁺](i) were inhibited by the mGluR antagonist S-MCPG. In the presence of NBQX, D-APV, pictrotoxin and TTX, bath application of the selective mGluR agonist 3,5-DHPG induced an elevation in [Na⁺](i) which extended over the whole dendritic field of the Purkinje cell. This finding demonstrates that the mGluR₁-mediated postsynaptic current leads to a significant influx of sodium into the dendritic cytoplasm of Purkinje cells and thereby provides a novel intracellular signalling mechanism that might be involved in mGluR₁-dependent synaptic plasticity at this synapse.