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.