Mutations in the alpha 1 subunit of an L-type voltage-activated Ca2+ channel cause myotonia in Caenorhabditis elegans

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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 αl 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.