limited by the speed of G protein activation. The reuptake/degradation of the neurotransmitter and the limited space for diffusion may affect the amplitude of the slow IPSC, thus regulating the degree of inhibition. In the hippocampus, generation of the slow IPSC is important for regulating the rhythmic activity of the network119. In midbrain DA neurons, slow activation of GIRKs via D2 receptors originates from local pooling of dendrodendritically released DA114,122. Future studies are needed to demonstrate a physiological role for the slow IPSC in vivo. In addition to postsynaptic activation, recent characterizations of GABAB receptor mediated presynaptic inhibition has revealed a component that is sensitive to a GIRK-specific channel inhibitor tertiapin123, suggesting a presynaptic role for GIRK channels in inhibiting neurotransmitter release2,124,125. Thus, GABA may inhibit pre-synaptic release concurrent with postsynaptic hyperpolarization.
