Extracellular calcium controls the dynamic range of neuronal metabotropic glutamate receptor responses

The metabotropic glutamate receptors (mGluRs) are neurotransmitter receptors important for synaptic plasticity in the brain. Here we report that native mGluR-mediated neuronal responses to glutamate are profoundly modulated by extracellular calcium (Ca_o²⁺). In mouse cerebellar Purkinje cells (PCs), Ca_o²⁺ drastically broadened the effective dose range for glutamate analogs in which native mGluR1-mediated cation current and intracellular Ca²⁺ mobilization were evoked. This effect has not been observed for recombinant mGluRs expressed in the heterologous cell systems. Ca_o²⁺ also drastically augmented these native mGluR-mediated responses to the glutamate analog. These Ca_o²⁺ effects were observed in both the wild-type mice and the mutant mice expressing mGluR1 specifically in their PCs, suggesting that the native mGluR1 in the PCs but not those in other cell types are the key mediators of the effects. These findings demonstrate that Ca_o²⁺ plays an important role in regulating native mGluR-mediated neuronal responses.