Dual signaling by mGluR5a results in bi‐directional modulation of N‐type Ca 2+ channels

We have studied how N‐type Ca 2+ channels are modulated by the metabotropic glutamate receptor 5a (mGluR5a) in Xenopus oocytes . Stimulation of the receptor with glutamate initiated two parallel responses, a rapid inhibition followed by an upregulation of the Ca 2+ current. Although a subsequent stimulation did not upregulate the Ca 2+ current, it did still produce a reduction in the amplitude of the current. The upregulation of Ca 2+ channels was prevented by the protein kinases inhibitor staurosporine and it was mimicked by the activation of PKC with phorbol esters. In contrast, the inhibition of the Ca 2+ current was insensitive to staurosporine. These results show that mGluR5a exerts a bi‐directional influence on Ca 2+ channels, which may explain how group I mGluRs facilitate and inhibit glutamate release at central synapses.