To identify molecular mechanisms that function in G-protein signaling, we have performed molecular genetic studies of a simple behavior of the nematodeCaenorhabditis elegans, egg laying, which is driven by a pair of serotonergic neurons, the hermaphrodite-specific neurons (HSNs). The activity of the HSNs is regulated by the G_o-coupled receptor EGL-6, which mediates inhibition of the HSNs by neuropeptides. We report here that this inhibition requires one of three inwardly rectifying K⁺channels encoded by theC. elegansgenome: IRK-1. Using ChannelRhodopsin-2-mediated stimulation of HSNs, we observed roles foregl-6andirk-1in regulating the excitability of HSNs. Althoughirk-1is required for inhibition of HSNs by EGL-6 signaling, we found that other G_osignaling pathways that inhibit HSNs involveirk-1little or not at all. These findings suggest that the neuropeptide receptor EGL-6 regulates the potassium channel IRK-1 via a dedicated pool of G_onot involved in other G_o-mediated signaling. We conclude that G-protein-coupled receptors that signal through the same G-protein in the same cell might activate distinct effectors and that specific coupling of a G-protein-coupled receptor to its effectors can be determined by factors other than its associated G-proteins.