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

J Physiol. 1997 Feb 15;499 ( Pt 1)(Pt 1):87-104. doi: 10.1113/jphysiol.1997.sp021913.

Abstract

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.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Amygdala / drug effects*
  • Animals
  • Calcium / metabolism*
  • Dose-Response Relationship, Drug
  • Ion Transport / physiology*
  • Male
  • Quisqualic Acid / pharmacology*
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, Metabotropic Glutamate / drug effects*
  • Sodium / metabolism*

Substances

  • Receptors, Metabotropic Glutamate
  • Quisqualic Acid
  • Sodium
  • Calcium