title: Hallmarks of the channelopathies associated with L-type calcium channels: a focus on the Timothy mutations in Ca(v)1.2 channels.
abstract: Within the voltage-gated calcium channels (Cav channels) family, there are four genes coding for the L-type Cav channels (Cav1). The Cav1 channels underly many important physiological functions like excitation-contraction coupling, hormone secretion, neuronal excitability and gene transcription. Mutations found in the genes encoding the Cav channels define a wide variety of diseases called calcium channelopathies and all four genes coding the Cav1 channels are carrying such mutations. L-type calcium channelopathies include muscular, neurological, cardiac and vision syndromes. Among them, the Timothy syndrome (TS) is linked to missense mutations in CACNA1C, the gene that encodes the Ca(v)1.2 subunit. Here we review the important features of the Cav1 channelopathies. We also report on the specific properties of TS-Ca(v)1.2 channels, which display non-inactivating calcium current as well as higher plasma membrane expression. Overall, we conclude that both electrophysiological and surface expression properties must be investigated to better account for the functional consequences of mutations linked to calcium channelopathies.
authors.affiliation: CNRS, UMR-5203, Institut de Génomique Fonctionnelle, Montpellier, France.
authors.forename: Isabelle
authors.initials: I
authors.lastname: Bidaud
authors.forename: Philippe
authors.initials: P
authors.lastname: Lory
mesh_terms: D000818:Animals; D001321:Autistic Disorder; D015220:Calcium Channels / Q000235:genetics; D020746:Calcium Channels, L-Type / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D002462:Cell Membrane / Q000378:metabolism; D053447:Channelopathies / Q000235:genetics* / Q000503:physiopathology; D006801:Humans; D020514:Hypokalemic Periodic Paralysis / Q000235:genetics; D008133:Long QT Syndrome / Q000235:genetics*; D008564:Membrane Potentials; D020125:Mutation, Missense; D011487:Protein Conformation; D021381:Protein Transport; D013576:Syndactyly / Q000235:genetics*
chemical_list: C412223:CACNA1S protein, human; D015220:Calcium Channels; D020746:Calcium Channels, L-Type; C419385:L-type calcium channel alpha(1C)