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Neurosteroid-GABAA receptor interactions

The influence of GABAA receptor subunit composition on the GABA-modulatory effects of pregnane steroids has been investigated by partner 4 using the Xenopus laevis oocyte expression system and the two electrode voltage clamp technique. Studies of the interactions of 3a, 5a-tetrahydroprogesterone with 14 different GABAA receptor isoforms have been completed show the subunit composition to be an important determinant of neurosteroid action. The subunit composition of GABAA receptors may thus contribute to their neuronal specificity and behavioural profile.

An important finding was that not only the subunit composition, but also phosporylation by protein kinase C (PKC) could influence the interaction of pregnane steroids with synaptic GABAA receptors. The interaction of neurosteroids with GABAA receptors is brain region and indeed neurone dependent and the activity of neuronal kinases contribute to this heterogeneity, and potentially provide a mechanism to dynamically influence the actions of neurosteroids.

Experimental evidence showed that the PKCe isoform is involved in governing the neurosteroid/ GABAA receptor interactions. The molecular interactions of the PKCe with GABAA receptor subunits is currently under investigation.

Reported by

University of Dundee
Ninewells Hospital and Medical School
DD1 9SY Dundee
United Kingdom
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