Quisqualate‐preferring metabotropic glutamate receptor activates Na(+)‐Ca2+ exchange in rat basolateral amygdala neurones.

1. Inward currents evoked by metabotropic glutamate receptor (mGlu) agonists quisqualate and 1S,3R‐1‐aminocyclopentane‐1,3‐dicarboxylic acid (1S,3R‐ACPD) were characterized in the basolateral nucleus of the amygdala. Currents were recorded with whole‐cell patch electrodes in the presence of D‐2‐amino‐5‐phosphonovaleric acid (D‐APV, 50 microM), 6‐cyano‐7‐nitro‐quinoxaline‐2,3‐dione (CNQX, 30 microM) and tetrodotoxin (TTX, 1 microM). 2. When recording with K+ electrodes, quisqualate (10‐50 microM) produced an inward current which was not associated with a significant change in membrane slope conductance (Gm) and was insensitive to Ba2+ (0.2 mM) and Cs+ (2 mM). The 1S,3R‐ACPD (50‐200 microM)‐induced inward current was associated with a decreased Gm and reversed polarity around ‐95 mV. However, in Ba2+ and Cs+, the 1S,3R‐ACPD inward current amplitude was enhanced and was not accompanied by a change in Gm, a response similar to that evoked by quisqualate. 3. Glutamate (1 mM) and the group I mGlu specific agonist (S)‐3,5‐dihydroxyphenylglycine (DHPG, 100 microM) also evoked currents not associated with a change in Gm. 4. When recorded with Cs+ electrodes in external Ba2+ and Cs+ solution, quisqualate activated an inward current more potently than 1S,3R‐ACPD, suggesting that this current is preferentially activated by quisqualate. The mGlu agonist‐induced inward current was not accompanied by a Gm change under these conditions. 5. Substitution of extracellular Na+ with Li+ (117 or 50 mM) or with 100 mM choline reduced the quisqualate‐ and 1S,3R‐ACPD‐induced inward currents, results consistent with mediation by Na(+)‐Ca2+ exchange. 6. The quisqualate‐ and 1S,3R‐ACPD‐induced inward currents were reduced in Ca(2+)‐free EGTA (1 mM) solution and prevented by including the Ca2+ chelating agent BAPTA (10 mM) in the recording electrode. In low‐Ca2+ (100 microM)‐ and Cd2+ (200 microM)‐containing solution to block voltage‐gated Ca2+ currents, the quisqualate‐induced current was not altered, but the 1S,3R‐ACPD inward current was blocked. These data suggest that the quisqualate‐ and 1S,3R‐ACPD‐induced currents are mediated through a rise in intracellular Ca2+ and require extracellular Ca2+, but that the 1S,3R‐ACPD current may depend on Ca2+ influx via voltage‐gated Ca2+ channels. 7. The quisqualate current with no Gm change was inhibited by including the Na(+)‐Ca2+ exchange inhibitory peptide (XIP; 10 microM) in the K+ recording electrode. XIP did not prevent the outward current evoked by baclofen (10 microM) or the 1S,3R‐ACPD‐induced inward current associated with decreased conductance. 8. These data are consistent with the hypothesis that quisqualate and 1S,3R‐ACPD in Ba2+ and Cs+ solution activate a Na(+)‐Ca2+ exchange current not associated with a conductance change. The quisqualate exchange current mediated through a group I mGlu may result from mobilization of Ca2+ from intracellular stores. The 1S,3R‐ACPD exchange current requires extracellular Ca2+ passing through voltage‐gated Ca2+ channels and may be mediated through a different receptor.