The GAR-3 muscarinic receptor cooperates with calcium signals to regulate muscle contraction in the Caenorhabditis elegans pharynx.
Muscarinic acetylcholine receptors regulate the activity of neurons and muscle cells through G-protein-coupled cascades. Here, we identify a pathway through which the GAR-3 muscarinic receptor regulates both membrane potential and excitation-contraction coupling in the Caenorhabditis elegans pharyngeal muscle. GAR-3 signaling is enhanced in worms overexpressing gar-3 or lacking GPB-2, a G-protein beta-subunit involved in RGS-mediated inhibition of G(o)alpha- and G(q)alpha-linked pathways. High levels of signaling through GAR-3 inhibit pharyngeal muscle relaxation and impair feeding--but do not block muscle repolarization--when worms are exposed to arecoline, a muscarinic agonist. Loss of gar-3 function results in shortened action potentials and brief muscle contractions in the pharyngeal terminal bulb. High levels of calcium entry through voltage-gated channels also impair terminal bulb relaxation and sensitize worms to the toxic effects of arecoline. Mutation of gar-3 reverses this sensitivity, suggesting that GAR-3 regulates calcium influx or calcium-dependent processes. Because the effects of GAR-3 signaling on membrane depolarization and muscle contraction can be separated, we conclude that GAR-3 regulates multiple calcium-dependent processes in the C. elegans pharyngeal muscle.
Steger
Katherine A
KA
Department of Molecular Biology, University of Texas Southwestern Medical Center, Dallas, Texas 75390-9148, USA.
Avery
Leon
L
D000595:Amino Acid Sequence; D000818:Animals; D030801:Animals, Genetically Modified; D017173:Caenorhabditis elegans / Q000235:genetics*; D029742:Caenorhabditis elegans Proteins / Q000235:genetics* / Q000502:physiology; D020013:Calcium Signaling / Q000502:physiology*; D005091:Exons / Q000235:genetics; D049452:Green Fluorescent Proteins / Q000235:genetics; D007438:Introns / Q000235:genetics; D008969:Molecular Sequence Data; D009119:Muscle Contraction / Q000502:physiology*; D009474:Neurons / Q000502:physiology; D010614:Pharynx / Q000294:innervation; D017354:Point Mutation; D011976:Receptors, Muscarinic / Q000235:genetics* / Q000502:physiology; D017384:Sequence Deletion; D017386:Sequence Homology, Amino Acid
D029742:Caenorhabditis elegans Proteins; C477876:GAR-3 protein, C elegans; D011976:Receptors, Muscarinic; D049452:Green Fluorescent Proteins