GABA_B Receptors Couple to Gα_q to Mediate Increases in Voltage-Dependent Calcium Current During Development

Authors

Andrew S. Karls, Marquette University
Michelle Mynlieff, Marquette UniversityFollow

Document Type

Article

Language

eng

Publication Date

10-2015

Publisher

Wiley

Source Publication

Journal of Neurochemistry

Source ISSN

1471-4159

Original Item ID

DOI: 10.1111/jnc.13259

Abstract

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.

Comments

Accepted version. Journal of Neurochemistry, Vol. 135, No. 1 (October 2015): 88-100. DOI. © 2015 International Society for Neurochemistry. Used with permission.

This is the peer reviewed version of the following article: "GABA_B Receptors Couple to Gα_q to Mediate Increases in Voltage-Dependent Calcium Current During Development," Journal of Neurochemistry, Vol. 135, No. 1 (October 2015): 88-100, which has been published in final form at DOI. This article may be used for non-commercial purposes in accordance With Wiley Terms and Conditions for self-archiving

Recommended Citation

Karls, Andrew S. and Mynlieff, Michelle, "GABA_B Receptors Couple to Gα_q to Mediate Increases in Voltage-Dependent Calcium Current During Development" (2015). Biological Sciences Faculty Research and Publications. 512.
https://epublications.marquette.edu/bio_fac/512