MUTATIONS IN THE ALPHA-1 SUBUNIT OF AN L-TYPE VOLTAGE-ACTIVATED CA2-ELEGANS( CHANNEL CAUSE MYOTONIA IN CAENORHABDITIS)

The control of excitable cell action potentials is central to animal b ehavior, Ne show that the egl-19 gene plays a pivotal role in regulati ng muscle excitation and contraction in the nematode Caenorhabditis el egans and encodes the alpha I subunit of a homologue of vertebrate L-t ype voltage-activated Ca2+ channels, Semidominant, gain-of-function mu tations in egl-19 cause myotonia: mutant muscle action potentials are prolonged and the relaxation delayed, Partial loss-of-function mutatio ns cause slow muscle depolarization and feeble contraction, The most s evere lass-of-function mutants lack muscle contraction and die as embr yos. We localized two myotonic mutations in the sixth membrane-spannin g domain of the first repeat (IS6) region, which has been Shown to be responsible for voltage-dependent inactivation, A third myotonic mutat ion implicates IIIS4, a region involved in sensing plasma-membrane vol tage change, in the inactivation process.