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 (Ca 2+ ) 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 Ca 2+ levels nor did it inhibit the action of 1S,3R ACPD. These results suggest that the responses in both cell types are mediated by mGlu5 receptors. In the absence of extracellular Ca 2+ ions, 1S,3R ACPD (100 μ m ) induced only a transient Ca 2+ response which decayed to baseline with a time constant of approximately 20 s in both cell types. Subsequent readdition of Ca 2+ (2 m m ) to the external solution in the continued presence of 1S,3R ACPD induced a sustained Ca 2+ plateau. The sustained Ca 2+ plateau could be blocked by a number of inorganic cations, with an order of potency of Zn 2+ La 3+ >Cd 2+ Co 2+ >Ni 2+ >Mg 2+ . Similar concentrations of Zn 2+ had little effect on Ca 2+ ‐influx evoked by 25 m m K + . It is concluded that the Ca 2+ ‐entry pathway activated by mGlu5 receptors resembles store‐operated Ca 2+ ‐entry pathways that have been described in other cell types.British Journal of Pharmacology (1998) 125 , 1551–1561; doi: 10.1038/sj.bjp.0702203