Document Type

Article

Language

eng

Format of Original

13 p.

Publication Date

10-2015

Publisher

Wiley

Source Publication

Journal of Neurochemistry

Source ISSN

1471-4159

Original Item ID

DOI: 10.1111/jnc.13259, PubMed Central: PMID26212383

Abstract

Metabotropic GABAB receptors are known to modulate the activity of voltage-dependent calcium channels. Previously, we have shown that GABAB 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 GABAB-mediated enhancement of calcium influx. When Gαq G-proteins were eliminated using morpholino-mediated knockdown, the enhancing effects of the GABAB receptor agonist baclofen (10 μM) on calcium current or entry were eliminated. These data suggest that GABAB receptors couple to Gαq to regulate calcium influx. Confocal imaging analysis illustrating colocalization of GABAB 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 GABAB 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.

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: "GABAB Receptors Couple to Gαq 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

Available for download on Saturday, October 01, 2016

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