Inherited Ventricular Arrhythmias: The Role of the Multi-Subunit Structure of the L-Type Calcium Channel Complex.
The normal heartbeat is conditioned by transient increases in the intracellular free Ca2+concentration. Ca2+influx in cardiomyocytes is regulated by the activity of the heteromeric L-type voltage-activated CaV1.2 channel. A complex network of interactions between the different proteins forming the ion channel supports the kinetics and the activation gating of the Ca2+influx. Alterations in the biophysical and biochemical properties or in the biogenesis in any of these proteins can lead to serious disturbances in the cardiac rhythm. The multi-subunit nature of the channel complex is better comprehended by examining the high-resolution three-dimensional structure of the closely related CaV1.1 channel. The architectural map identifies precise interaction loci between the different subunits and paves the way for elucidating the mechanistic basis for the regulation of Ca2+balance in cardiac myocytes under physiological and pathological conditions.
Département de Pharmacologie et Physiologie, Faculté de Médecine, Institut Cardiologie de Montréal, Université de Montréal, 5000 Bélanger, Montréal, QC, H1T 1C8, Canada.
Julie
J
Briot
Département de Pharmacologie et Physiologie, Faculté de Médecine, Institut Cardiologie de Montréal, Université de Montréal, 5000 Bélanger, Montréal, QC, H1T 1C8, Canada.
Marie-Philippe
MP
Tétreault
Département de Pharmacologie et Physiologie, Faculté de Médecine, Institut Cardiologie de Montréal, Université de Montréal, 5000 Bélanger, Montréal, QC, H1T 1C8, Canada.
Benoîte
B
Bourdin
Département de Pharmacologie et Physiologie, Faculté de Médecine, Institut Cardiologie de Montréal, Université de Montréal, 5000 Bélanger, Montréal, QC, H1T 1C8, Canada. lucie.parent@umontreal.ca.
Lucie
L
Parent
D000200:Action Potentials; D000818:Animals; D001145:Arrhythmias, Cardiac / Q000235:genetics / Q000378:metabolism* / Q000503:physiopathology; D020746:Calcium Channels, L-Type / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D020013:Calcium Signaling / Q000235:genetics; D020022:Genetic Predisposition to Disease; D006339:Heart Rate / Q000235:genetics; D006801:Humans; D015640:Ion Channel Gating; D007700:Kinetics; D008958:Models, Molecular; D009154:Mutation; D010641:Phenotype; D055503:Protein Multimerization; D020836:Protein Structure, Quaternary; D021122:Protein Subunits; D013329:Structure-Activity Relationship
C079146:CACNA1C protein, human; D020746:Calcium Channels, L-Type; D021122:Protein Subunits
CACNA2D1; Cardiac Arrhythmias; Posttranslational Modifications; Structural Biology