Much of the interplay of excitatory and inhibitory signals required for normal neuronal function occurs in the dendrites of neurons1. Detailed electron and light microscopic studies show that fast excitatory inputs are mediated by ionotropic glutamate receptors such as NMDARs and AMPARs that are located in the postsynaptic density at the head of the spine, whereas inhibitory synapses typically form on the soma and dendritic shafts1. The fast inhibitory signals are mediated by ionotropic GABAA/glycine receptors. In addition to this fast inhibition, a slower inhibitory postsynaptic potential (sIPSC) exists that is mediated by G protein-activated inwardly rectifying potassium (GIRK or Kir3) channels that are located perisynaptically outside the postsynaptic density in the spine and also on the shaft2. This review discusses recent findings on the physiology, function and dysfunction of GIRK channels in the brain.
