IRK-1 Potassium Channels Mediate Peptidergic Inhibition ofCaenorhabditis elegansSerotonin Neurons via a G_oSignaling Pathway

Abstract

To identify molecular mechanisms that function in G protein signaling, we have performed molecular genetic studies of a simple behavior of the nematode C. elegans, egg laying, which is driven by a pair of serotonergic neurons, the HSNs. The activity of the HSNs is regulated by the Go-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 the C. elegans genome: IRK-1. Using ChannelRhodopsin2-mediated stimulation of HSNs, we observed roles for egl-6 and irk-1 in regulating the excitability of HSNs. Although irk 1 is required for inhibition of HSNs by EGL-6 signaling, we found that other Go signaling pathways that inhibit HSNs involve irk-1 little or not at all. These findings suggest that the neuropeptide receptor EGL-6 regulates the potassium channel IRK 1 is via a dedicated pool of Go not involved in other Go-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 GPCR to its effectors can be determined by factors other than its associated G proteins.

Illuminating neural circuits and behaviour in Caenorhabditis elegans with optogenetics

“…ChR2-mediated stimulation of HSN, which induces egg laying, has been used to identify roles of potassium channels in regulating HSN excitability [42,90].…”

Environmental CO 2 inhibits Caenorhabditis elegans egg-laying by modulating olfactory neurons and evokes widespread changes in neural activity

“…The HSNs are critical regulators of egg-laying and link the egg-laying circuit to the rest of nervous system (54). Ca 2+ spikes in HSNs correlate with and likely trigger egg-laying events (55), because optogenetic stimulation of HSNs is sufficient to drive egg-laying (56)(57)(58). Does inhibition of egglaying by elevated CO 2 involve inhibition of HSN motor neurons?…”

Neurotransmitter signaling through heterotrimeric G proteins: insights from studies in C. elegans

“…Such mutants were used to originally discover and subsequently characterize the Regulators of G protein Signaling (RGS proteins) that inhibit most neural G protein signaling in C. elegans and in mammals (Koelle and Horvitz, 1996; PMID 8548815; Hajdu-Cronin et al, 1999: PMID 10421631). The neural circuit that controls egg laying is particularly simple and well-characterized, and tools to express transgenes in any cell of the circuit, to monitor activity of the circuit in freely-behaving animals with the fluorescent Ca 2+ indicator GCaMP, and to optogenetically manipulate the circuit have all been developed (Schafer, 2006: PMID 17094742; Emtage et al, 2012: PMID 23152612; Collins and Koelle, 2013: PMID 23303953).…”

“…The only study of Gβγ effectors in C. elegans showed that when the EGL-6 neuropeptide receptor activates Gα o in the HSN neurons, the resulting inhibition of egg laying requires IRK-1, a homolog of mammalian Gβγ-activated K + channels, and that no other such K + channel is required (Emtage et al, 2012: PMID 23152612). However, this same study also demonstrated that IRK-1 does not mediate inhibition of egg laying when other methods are used to activate Gα o , suggesting that other effectors besides K + channels must mediate Gα o signaling.…”

“…When electrophysiological measurements have been used to measure signaling outcomes, the focus has been on the regulation of specific ion channels by Gβγ subunits (Reuveny et al, 1994: PMID 8022483; Herlitze et al, 1996: PMID 8637576), and indeed some of the effects of neural G protein signaling in C. elegans are mediated by such ion channels (Emtage et al, 2012: PMID 23152612). When effects on long-term memories have been the readout of signaling, the focus has been on the lasting effects of neural G protein signaling on synaptic structure or on transcription (Kandel, 2004: PMID 16134023).…”