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

<jats:p> Using whole cell patch-clamp recordings, we pharmacologically characterized the voltage-gated Ca<jats:sup>2+</jats:sup> channel (VGCC) currents of chicken nucleus magnocellularis (NM) neurons using barium as the charge carrier. NM neurons possessed both low- and high-voltage-activated Ca<jats:sup>2+</jats:sup> channel currents (HVA I<jats:sub>Ba<jats:sup>2+</jats:sup></jats:sub>). The N-type channel blocker (ω-conotoxin-GVIA) inhibited more than half of the total HVA I<jats:sub>Ba<jats:sup>2+</jats:sup></jats:sub>, 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 I<jats:sub>Ba<jats:sup>2+</jats:sup></jats:sub> was examined by bath application of glutamate (100 μM), which inhibited the HVA I<jats:sub>Ba<jats:sup>2+</jats:sup></jats:sub> 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 I<jats:sub>Ba<jats:sup>2+</jats:sup></jats:sub>. The nonspecific mGluR agonist, (1S,3R)-1-aminocyclopentane-1,3-dicarbosylic acid (1S,3R-ACPD), mimicked the inhibitory effect of glutamate on HVA I<jats:sub>Ba<jats:sup>2+</jats:sup></jats:sub>. 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<jats:sup>+</jats:sup> or Na<jats:sup>+</jats:sup> 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 Ca<jats:sup>2+</jats:sup> entry into these highly active NM neurons and regulates their Ca<jats:sup>2+</jats:sup> homeostasis. </jats:p>