The activation of GIRK channels can influence neuronal networks at different levels in the brain via different mechanisms: (1) neuronal self-inhibition – where the transmitter released from the dendrites activates the GIRK channels on the same cell (Bacci et al. 2004), (2) neuron-to-neuron inhibition – a result of activation of post synaptic receptors such as GABAB (Newberry & Nicoll 1985), D2 (Beckstead & Williams 2007) and group II metabotropic glutamate receptors (Dutar et al. 1999) by the relevant transmitters released from presynaptic neurons and (3) network level inhibition – a result of ambient levels of neuromodulators like adenosine and somatostatin, which are endogenous G protein coupled receptor agonists. Somatostatin may alter the oscillatory behavior of thalamic networks through postsynaptic activation of GIRK channels together with presynaptic inhibition (Sun et al. 2002); in addition, endogenous adenosine may suppress gamma oscillations in the hippocampus, which also activate GIRK channels (Pietersen et al. 2009).
