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Conditional Regulation of Neurosteroid Sensitivity of GABAA Receptors
Department of Experimental Neurophysiology, Research Institute for Neurosciences, Faculty of Earth and Life Sciences, Vrije Universiteit Amsterdam, 1081 HV Amsterdam, the Netherlands
Address for correspondence: Prof. Dr. A.B. Brussaard, Department of Experimental Neurophysiology, Vrije Universiteit Amsterdam, de Boelelaan 1085,1081 HV Amsterdam, the Netherlands Voice: +31 20 444 7098; fax: + 31 20 444 7112. brssrd{at}cner.vu.nl Ann. N.Y. Acad. Sci 1007: 29-36 (2003).
Nongenomic gonadal steroid feedback to oxytocin containing neurons in the supraoptic nucleus of the hypothalamus is mediated via the neurosteroid allopregnanolone (3
 -OH-DHP) that acts as an allosteric modulator of the postsynaptic GABAA receptors. We found evidence to support the idea that neurosteroids not only potentiate GABAA receptor function but also prevent its suppression by PKC. In addition, we found that neurosteroid sensitivity of GABAA receptor itself is dependent on the balance between endogenous phosphatase and PKC activity and not, as previously suggested, on subunit composition changes of the GABAA receptor. These data imply that native GABAA receptors are only sensitive to 3-OH-DHP if there is endogenous phosphatase activity. In contrast, when, due to endogenous release of oxytocin in the hypothalamus, the intracellular balance is shifted from high phosphatase activity toward a higher level of PKC-dependent phosphorylation, this leads to 3-OH-DHP-insensitivity of the GABAA receptors. How the regulatory mechanisms of the GABAA receptor physiology for the hypothalamus may also account for alterations in GABA transmission observed in other brain areas is discussed.
Key Words: GABAA receptor • lactation • parturition • synaptic plasticity • oxytocin • progesterone-metabolite • allopregnanolone • PKC • phosphatases This article has been cited by other articles:
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