Type-A GABA receptors are vitally important for brain function. They provide a dampening mechanism for neural excitation across the CNS. Inhibitory neurosteroids are naturally synthesised in the brain and released where they can modulate GABA-A receptors and thus brain physiology. Recent analysis suggests that these neurosteroids may bind within the receptor’s transmembrane domain, with an ion channel location also being proposed. To date the exact location, and there may be more than one, remain unknown. Here, we will use electrophysiology coupled with molecular and structural biology to locate these important sites thereby enabling their physiological relevance to be identified.
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