Rapid action of stress hormones and the role of the mineralocorticoid receptor.

Femke Groeneweg

Corticosteroids are known to affect neuronal activity and behaviour within a few minutes. This action cannot be attributed to the genomic role of the two known receptors; the glucocorticoid (GR) and mineralocorticoid (MR) receptors. Recently, it was found that one of these receptors, the MR is actually involved in the fast actions of corticosteroids, but in an alternative membrane-associated form.

In this project we aim to elucidate this rapid, membrane-associated role of the MR.
What molecular pathways are involved in this response? How does the MR translocate to the membrane? How do the different stress phases work together? And, can we find functional (behavioural) correlates for these acute stress effects that also require the MR?
To answer these questions we will use several models. In collaboration with Utrecht University, we established an electrophysiological model in neuronal-like cells, studying the effect of corticosterone on potassium currents. Additionally, we will try to visualize the MR membrane localization by a fluorescent microscopy method (TIRF microscopy). And we will use behavioural models in mice to study the fast actions of stress hormones in vivo.