Calcium dependence of native metabotropic glutamate receptor signaling in central neurons

Metabotropic glutamate receptors (mGluRs) are G protein-coupled receptors that are distributed throughout the brain and play important roles in regulation of synaptic efficacy. Some studies report that mGluRs heterologously expressed in nonneuronal cells are sensitive not only to glutamate but also to extracellular Ca²⁺ (Ca²⁺_o). We studied the Ca²⁺_o-sensitivity of native mGluRs in mammalian central neurons. In cerebellar Purkinje cells that naturally express type-1 mGluR (mGluR1), physiological levels of Ca²⁺_o (around 2 mM) activate mGluR1-mediated intracellular Ca²⁺ mobilization. The activation of the native mGluR1 response to Ca²⁺_o appears to be slower than that to glutamate. Ca²⁺_o (2 mM) also augments glutamate analog-evoked, native mGluR1-mediated inward cation current and intracellular Ca²⁺_o mobilization. Detailed analysis of this effect suggests that Ca²⁺_o modulates the glutamate responsiveness of native and heterologously expressed mGluR1s in different manners. These findings suggest that Ca²⁺_o may enhance the basal level and glutamate responsiveness of neuronal mGluR signaling in vivo.