Activation of Metabotropic Glutamate Receptors Inhibits High-Voltage-Gated Calcium Channel Currents of Chicken Nucleus Magnocellularis Neurons

Abstract

Using whole cell patch-clamp recordings, we pharmacologically characterized the voltage-gated Ca2+ channel (VGCC) currents of chicken nucleus magnocellularis (NM) neurons using barium as the charge carrier. NM neurons possessed both low- and high-voltage-activated Ca2+ channel currents (HVA IBa2+). The N-type channel blocker (ω-conotoxin-GVIA) inhibited more than half of the total HVA IBa2+, whereas blockers of L- and P/Q-type channels each inhibited a small fraction of the current. Metabotropic glutamate receptor (mGluR)-mediated modulation of the HVA IBa2+ was examined by bath application of glutamate (100 μM), which inhibited the HVA IBa2+ by an average of 16%. The inhibitory effect was dose dependent and was partially blocked by ω-conotoxin-GVIA, indicating that mGluRs modulate N and other type HVA IBa2+. The nonspecific mGluR agonist, (1S,3R)-1-aminocyclopentane-1,3-dicarbosylic acid (1S,3R-ACPD), mimicked the inhibitory effect of glutamate on HVA IBa2+. Group I–III mGluR agonists showed inhibition of the HVA current with the most potent being the group III agonist l(+)-2-amino-4-phosphonobutyric acid. 1S,3R-ACPD (200 μM) had no effect on K+ or Na+ currents. The firing properties of NM neurons were also not altered by 1S,3R-ACPD. We propose that the inhibition of VGCC currents by mGluRs limits depolarization-induced Ca2+ entry into these highly active NM neurons and regulates their Ca2+ homeostasis.