G protein-gated inwardly rectifying K+ (GIRK/Kir3) channels mediate the G protein-dependent, postsynaptic inhibitory effects of many neurotransmitters in the central nervous system, including GABA, dopamine, serotonin, acetylcholine, and glutamate1. GIRK channels are found almost exclusively in the somato-dendritic compartment and are enriched near excitatory synapses in spines2. Thus, these channels are well-positioned to temper the influence of excitatory input on neuronal activity3. Genetic and pharmacological investigations in mice have revealed important roles for GIRK channels in diverse settings, including seizures, learning/memory, nociception/analgesia, anxiety, and addiction4–6.
