Premium
Mutations in the α1 subunit of an L‐type voltage‐activated Ca 2+ channel cause myotonia in Caenorhabditis elegans
Author(s) -
Lee Raymond Y.N.,
Lobel Leslie,
Hengartner Michael,
Horvitz H.Robert,
Avery Leon
Publication year - 1997
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.1093/emboj/16.20.6066
Subject(s) - biology , caenorhabditis elegans , myotonia , mutant , depolarization , microbiology and biotechnology , protein subunit , g alpha subunit , muscle contraction , membrane potential , genetics , biophysics , gene , anatomy , myotonic dystrophy
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 Ca 2+ 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.