GABA B receptors couple to Gα q to mediate increases in voltage‐dependent calcium current during development
| Autor: | Andrew S. Karls, Michelle Mynlieff |
|---|---|
| Rok vydání: | 2015 |
| Předmět: |
Baclofen
medicine.medical_specialty chemistry.chemical_element Calcium Hippocampus Biochemistry Article Membrane Potentials Rats Sprague-Dawley 03 medical and health sciences Cellular and Molecular Neuroscience 0302 clinical medicine Internal medicine medicine Animals L-type calcium channel Receptor GABA Agonists Protein kinase C 030304 developmental biology Neurons 0303 health sciences Voltage-dependent calcium channel biology T-type calcium channel Cell biology Endocrinology Metabotropic receptor Receptors GABA-B nervous system chemistry Gq alpha subunit Gene Knockdown Techniques biology.protein GTP-Binding Protein alpha Subunits Gq-G11 Calcium Channels 030217 neurology & neurosurgery |
| Zdroj: | Journal of Neurochemistry. 135:88-100 |
| ISSN: | 1471-4159 0022-3042 |
| Popis: | 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-Gi/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. Gαq was knocked down using morpholino oligonucleotides prior to examining GABA(B) -mediated enhancement of calcium influx. When Gαq 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 Gαq to regulate calcium influx. Confocal imaging analysis illustrating colocalization of GABA(B) receptors with Gαq 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 Gαq 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 Gi/o . In this study, knockdown of Gαq 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 Gq to activate PKCα leading to enhancement of L-type calcium current. |
| Databáze: | OpenAIRE |
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