FEBS Lett 2004 Oct 22;5763:428-32. doi: 10.1016/j.febslet.2004.09.053.

Dual signaling by mGluR5a results in bi-directional modulation of N-type Ca2+ channels.

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We have studied how N-type Ca2+ 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 Ca2+ current. Although a subsequent stimulation did not upregulate the Ca2+ current, it did still produce a reduction in the amplitude of the current. The upregulation of Ca2+ 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 Ca2+ current was insensitive to staurosporine. These results show that mGluR5a exerts a bi-directional influence on Ca2+ channels, which may explain how group I mGluRs facilitate and inhibit glutamate release at central synapses.

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