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

The control of excitable cell action potentials is central to animal behavior, Ne show that the egl-19 gene plays a pivotal role in regulating muscle excitation and contraction in the nematode Caenorhabditis elegans and encodes the alpha I subunit of a homologue of vertebrate L-type voltage-activated Ca2+ channels, Semidominant, 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 lass-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.