AUTHOR=Puia Giulia , Ravazzini Federica , Castelnovo Luca Franco , Magnaghi Valerio 

TITLE=PKCε and allopregnanolone: functional cross-talk at the GABAA receptor level

JOURNAL=Frontiers in Cellular Neuroscience

VOLUME=9

YEAR=2015

URL=https://www.frontiersin.org/journals/cellular-neuroscience/articles/10.3389/fncel.2015.00083

DOI=10.3389/fncel.2015.00083

ISSN=1662-5102

ABSTRACT=<p>Changes in GABAergic inhibition occur during physiological processes, during response to drugs and in various pathologies. These changes can be achieved through direct allosteric modifications at the γ-amino butyric acid (GABA) type A (GABA<sub>A</sub>) receptor protein level, or by altering the synthesis, trafficking and stability of the receptor. Neurosteroids (NSs) and protein kinase C (PKC) are potent modulators of GABA<sub>A</sub> receptors and their effects are presumably intermingled, even though evidence for this hypothesis is only partially explored. However, several PKC isoforms are able to phosphorylate the GABA<sub>A</sub> receptor, producing different functional effects. We focused on the ε isoform, that has been correlated to the sensitivity of the GABA<sub>A</sub> receptor to allosteric modulators and whose expression may be regulated in peripheral sensory neurons by NSs. The cross-talk between PKC-ε and NSs, leading to changes in GABA<sub>A</sub> receptor functionality, is considered and discussed in this perspective.</p>