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G protein-coupled inwardly rectifying potassium (GIRK) channels can be activated or inhibited by different classes of receptors, suggesting a role for G proteins in determining signaling specificity.

In this chapter, we describe advances in our understanding of GIRK channel function based on recent high-resolution atomic structures of inwardly rectifying K (+) channels discussed in the context of classical structure-function experiments.

G-protein-gated inwardly rectifying potassium (GIRK) channels are important for determining neuronal excitability. In addition to G proteins, GIRK channels are potentiated by membrane cholesterol, which is elevated in the brains of people with neurodegenerative diseases such as Alzheimer’s dementia and Parkinson’s disease.

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