GABA B receptors couple to Gα q to mediate increases in voltage‐dependent calcium current during development

Metabotropic GABA B receptors are known to modulate the activity of voltage‐dependent calcium channels. Previously, we have shown that GABA B receptors couple to a non‐G i/o G‐protein to enhance calcium influx through L‐type calcium channels by activating protein kinase C in neonatal rat hippocampal neurons. In this study, the components of this signaling pathway were investigated further. Gα q was knocked down using morpholino oligonucleotides prior to examining GABA B ‐mediated enhancement of calcium influx. When Gα q G‐proteins were eliminated using morpholino‐mediated knockdown, the enhancing effects of the GABA B receptor agonist baclofen (10 μM) on calcium current or entry were eliminated. These data suggest that GABA B receptors couple to Gα q to regulate calcium influx. Confocal imaging analysis illustrating colocalization of GABA B receptors with Gα q supports this hypothesis. Furthermore, baclofen treatment caused translocation of PKCα (protein kinase C α) but not PKCβ or PKCε, suggesting that it is the α isoform of PKC that mediates calcium current enhancement. Inhibition of calcium/calmodulin‐dependent kinase II did not affect the baclofen‐mediated enhancement of calcium levels. In summary, activation of GABA B receptors during development leads to increased calcium in a subset of neurons through Gα q signaling and PKCα activation without the involvement of calcium/calmodulin‐dependent kinase II.Activation of GABA B receptors in the neonatal rat hippocampus enhances voltage‐dependent calcium currents independently of G i/o . In this study, knockdown of Gα q with morpholino oligonucleotides abolished enhancement of calcium influx and protein kinase Cα was activated by GABA B receptors. Therefore, we hypothesize that GABA B receptors couple to G q to activate PKCα leading to enhancement of L‐type calcium current.