title: Mutations in the alpha1 subunit of an L-type voltage-activated Ca2+ channel cause myotonia in Caenorhabditis elegans.
abstract: The control of excitable cell action potentials is central to animal behavior. We show that the egl-19 gene plays a pivotal role in regulating muscle excitation and contraction in the nematode Caenorhabditis elegans and encodes the alphal subunit of a homologue of vertebrate L-type voltage-activated Ca2+ channels. Semi-dominant, gain-of-function mutations in egl-19 cause myotonia: mutant muscle action potentials are prolonged and the relaxation delayed. Partial loss-of-function mutations cause slow muscle depolarization and feeble contraction. The most severe loss-of-function mutants lack muscle contraction and die as embryos. We localized two myotonic mutations in the sixth membrane-spanning domain of the first repeat (IS6) region, which has been shown to be responsible for voltage-dependent inactivation. A third myotonic mutation implicates IIIS4, a region involved in sensing plasma-membrane voltage change, in the inactivation process.
authors.affiliation: Department of Molecular Biology and Oncology, University of Texas Southwestern Medical Center, Dallas, TX 75235-9148, USA.
authors.forename: R Y
authors.initials: RY
authors.lastname: Lee
authors.forename: L
authors.initials: L
authors.lastname: Lobel
authors.forename: M
authors.initials: M
authors.lastname: Hengartner
authors.forename: H R
authors.initials: HR
authors.lastname: Horvitz
authors.forename: L
authors.initials: L
authors.lastname: Avery
mesh_terms: D000200:Action Potentials / Q000235:genetics*; D000595:Amino Acid Sequence; D000818:Animals; D017173:Caenorhabditis elegans / Q000235:genetics*; D029742:Caenorhabditis elegans Proteins; D002118:Calcium / Q000494:pharmacology; D015220:Calcium Channels / Q000187:drug effects / Q000235:genetics*; D003001:Cloning, Molecular; D017238:Genes, Helminth; D005804:Genes, Lethal; D015801:Helminth Proteins / Q000235:genetics; D015640:Ion Channel Gating; D008969:Molecular Sequence Data; D009119:Muscle Contraction / Q000235:genetics; D009124:Muscle Proteins / Q000187:drug effects / Q000235:genetics*; D009126:Muscle Relaxation / Q000235:genetics; D009154:Mutation; D009222:Myotonia / Q000209:etiology / Q000235:genetics*; D017386:Sequence Homology, Amino Acid
chemical_list: D029742:Caenorhabditis elegans Proteins; D015220:Calcium Channels; C109164:Egl-19 protein, C elegans; D015801:Helminth Proteins; D009124:Muscle Proteins; D002118:Calcium