Group I metabotropic glutamate receptor-induced Ca(2+)-gradients in rat superficial spinal dorsal horn neurons

Here, we investigated changes in the free cytosolic Ca(2+) concentration ([Ca(2+)](i)), induced by the pharmacological activation of metabotropic glutamate receptors (mGluRs), in nociceptive neurons of the superficial spinal dorsal horn. Microfluorometric Ca(2+) 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 [Ca(2+)](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 [Ca(2+)](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 [Ca(2+)](i) increase. Depleting intracellular Ca(2+) stores with CPA or inhibiting IP(3)-receptors with 2-APB, respectively, reduced the (S)-3,5-DHPG-evoked [Ca(2+)](i) increase significantly. Inhibition of voltage-dependent L-type Ca(2+) channels (VDCCs) by verapamil or nicardipine reduced the (S)-3,5-DHPG-induced [Ca(2+)](i) rise likewise. Thus, in rat spinal cord, (S)-3,5-DHPG enhances Ca(2+) signalling in superficial dorsal horn neurons, mediated by the release of Ca(2+) from IP(3)-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.