title: The Brugada syndrome mutation A39V does not affect surface expression of neuronal rat Cav1.2 channels.
abstract: BACKGROUND
  A loss of function of the L-type calcium channel, Cav1.2, results in a cardiac specific disease known as Brugada syndrome. Although many Brugada syndrome channelopathies reduce channel function, one point mutation in the N-terminus of Cav1.2 (A39V) has been shown to elicit disease a phenotype because of a loss of surface trafficking of the channel. This lack of cell membrane expression could not be rescued by the trafficking chaperone Cavβ.
  
  
  RESULTS
  We report that despite the striking loss of trafficking described previously in the cardiac Cav1.2 channel, the A39V mutation while in the background of the brain isoform traffics and functions normally. We detected no differences in biophysical properties between wild type Cav1.2 and A39V-Cav1.2 in the presence of either a cardiac (Cavβ2b), or a neuronal beta subunit (Cavβ1b). In addition, the A39V-Cav1.2 mutant showed a normal Cavβ2b mediated increase in surface expression in tsA-201 cells.
  
  
  CONCLUSIONS
  The Brugada syndrome mutation A39V when introduced into rat brain Cav1.2 does not trigger the loss-of-trafficking phenotype seen in a previous study on the human heart isoform of the channel.
authors.affiliation: Department of Physiology and Pharmacology, Hotchkiss Brain Institute, University of Calgary, Calgary, Canada.
authors.forename: Brett A
authors.initials: BA
authors.lastname: Simms
authors.forename: Gerald W
authors.initials: GW
authors.lastname: Zamponi
mesh_terms: D000595:Amino Acid Sequence; D019943:Amino Acid Substitution / Q000235:genetics*; D000818:Animals; D053840:Brugada Syndrome / Q000235:genetics*; D020746:Calcium Channels, L-Type / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*; D002460:Cell Line; D002462:Cell Membrane / Q000378:metabolism*; D006801:Humans; D008969:Molecular Sequence Data; D009154:Mutation / Q000235:genetics*; D009474:Neurons / Q000378:metabolism*; D051381:Rats; D016415:Sequence Alignment
chemical_list: D020746:Calcium Channels, L-Type; C419385:L-type calcium channel alpha(1C)