Inhibition by inorganic ions of a sustained calcium signal evoked by activation of mGlu5 receptors in rat cortical neurons and glia

The effect of mGlu receptor agonists on intracellular calcium (Ca2+) in rat cortical neurons and glial cells was studied. The responses evoked consisted of two phases; an initial transient response followed by a sustained plateau. In both cell types the order of potency of group I mGlu receptor agonists was DHPG > 1S,3R ACPD > 3-HPG. The selective mGlu5 agonist CHPG elicited responses in both cell types as did S4C3-HPG which is thought to be an mGlu5 agonist at high concentrations. S4-CPG had no effect on intracellular Ca2+ levels nor did it inhibit the action of IS,3R ACPD. These results suggest that the responses in both cell types are mediated by mGlu5 receptors. In the absence of extracellular Ca2+ ions, 1S,3R ACPD (100 microM) induced only a transient Ca2+ response which decayed to baseline with a time constant of approximately 20 s in both cell types. Subsequent readdition of Ca2+ (2 mM) to the external solution in the continued presence of 1S,3R ACPD induced a sustained Ca2+ plateau. The sustained Ca2+ plateau could be blocked by a number of inorganic cations, with an order of potency of Zn2+ > or = La3+ > Cd2+ > or = Co2+ > Ni2+ > Mg2+. Similar concentrations of Zn2+ had little effect on Ca2+-influx evoked by 25 mM K+. It is concluded that the Ca2+-entry pathway activated by mGlu5 receptors resembles store-operated Ca2+-entry pathways that have been described in other cell types.