Group I metabotropic glutamate receptor-induced Ca2+-gradients in rat superficial spinal dorsal horn neurons

Here, we investigated changes in the free cytosolic Ca2+ concentration ([Ca2+]i), induced by the pharmacological activation of metabotropic glutamate receptors (mGluRs), in nociceptive neurons of the superficial spinal dorsal horn. Microfluorometric Ca2+ measurements with fura-2 in a lumbar spinal cord slice preparation from young rats were used.Bath application of the specific group I mGluR agonist (S)-3,5-dihydroxyphenylglycine ((S)-3,5-DHPG) resulted in a distinct increase of [Ca2+]i in most of the neurons in superficial dorsal horn. In contrast, activation of groups II or III mGluRs by DCG-IV or l-AP4, respectively, failed to evoke any significant change in [Ca2+]i. The effect of (S)-3,5-DHPG was mediated by both group I subtypes mGluR1 and mGluR5, since combined pre-treatment with the subtype antagonists (S)-4-CPG and MPEP was necessary to abolish the [Ca2+]i increase. Depleting intracellular Ca2+ stores with CPA or inhibiting IP3-receptors with 2-APB, respectively, reduced the (S)-3,5-DHPG-evoked [Ca2+]i increase significantly. Inhibition of voltage-dependent L-type Ca2+ channels (VDCCs) by verapamil or nicardipine reduced the (S)-3,5-DHPG-induced [Ca2+]i rise likewise.Thus, in rat spinal cord, (S)-3,5-DHPG enhances Ca2+ signalling in superficial dorsal horn neurons, mediated by the release of Ca2+ from IP3-sensitive intracellular stores and by an influx through L-type VDCCs. This may be relevant to the processing of nociceptive information in the spinal cord.