title: Calcium Channel Mutations in Cardiac Arrhythmia Syndromes.
abstract: Voltage gated calcium channels are essential for cardiac physiology by serving as sarcolemma- restricted gatekeepers for calcium in cardiac myocytes. Activation of the L-type voltagegated calcium channel provides the calcium entry required for excitation-contraction coupling and contributes to the plateau phase of the cardiac action potential. Given these critical physiological roles, subtle disturbances in L-type channel function can lead to fatal cardiac arrhythmias. Indeed, numerous human arrhythmia syndromes have been linked to mutations in the L-type channel leading to gain-of-function or loss-of-function mutations. In this review, we discuss the current state of knowledge regarding these mutations present in Timothy Syndrome, Long and Short QT Syndromes, Brugada Syndrome and Early Repolarization Syndrome. We discuss the pathological consequences of the mutations, the biophysical effects of the mutations on the channel as well as possible therapeutic considerations and challenges for future studies.
authors.forename: Matthew J
authors.initials: MJ
authors.lastname: Betzenhauser
authors.forename: Geoffrey S
authors.initials: GS
authors.lastname: Pitt
authors.affiliation: Lankenau Institute for Medical Research, 100 E. Lancaster Avenue. Wynnewood, PA 19096, USA. cantzelevitch@gmail.com.
authors.forename: Charles
authors.initials: C
authors.lastname: Antzelevitch
mesh_terms: D001145:Arrhythmias, Cardiac / Q000235:genetics* / Q000378:metabolism / Q000503:physiopathology; D001321:Autistic Disorder / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology; D053840:Brugada Syndrome / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology; D002118:Calcium / Q000378:metabolism; D020746:Calcium Channels, L-Type / Q000235:genetics* / Q000502:physiology; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D006801:Humans; D008133:Long QT Syndrome / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology; D008957:Models, Genetic; D009154:Mutation; D013576:Syndactyly / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology
chemical_list: D020746:Calcium Channels, L-Type; D002118:Calcium