title: Multilayered regulation of cardiac ion channels.
abstract: Essential to beat-to-beat heart function is the ability for cardiomyocytes to propagate electrical excitation and generate contractile force. Both excitation and contractility depend on specific ventricular ion channels, which include the L-type calcium channel (LTCC) and the connexin 43 (Cx43) gap junction. Each of these two channels is localized to a distinct subdomain of the cardiomyocyte plasma membrane. In this review, we focus on regulatory mechanisms that govern the lifecycles of LTCC and Cx43, from their biogenesis in the nucleus to directed delivery to T-tubules and intercalated discs, respectively. We discuss recent findings on how alternative promoter usage, tissue-specific transcription, and alternative splicing determine precise ion channel expression levels within a cardiomyocyte. Moreover, recent work on microtubule and actin-dependent trafficking for Cx43 and LTCC are introduced. Lastly, we discuss how human cardiac disease phenotypes can be attributed to defects in distinct mechanisms of channel regulation at the level of gene expression and channel trafficking. This article is part of a Special Issue entitled: Cardiomyocyte Biology: Cardiac Pathways of Differentiation, Metabolism and Contraction.
authors.affiliation: University of California, San Francisco, San Francisco, CA 94158, USA.
authors.forename: Shan-Shan
authors.initials: SS
authors.lastname: Zhang
authors.forename: Robin M
authors.initials: RM
authors.lastname: Shaw
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000378:metabolism; D017398:Alternative Splicing; D020746:Calcium Channels, L-Type / Q000235:genetics* / Q000378:metabolism; D002467:Cell Nucleus / Q000378:metabolism; D018031:Connexin 43 / Q000235:genetics* / Q000378:metabolism; D017629:Gap Junctions / Q000378:metabolism / Q000473:pathology; D005786:Gene Expression Regulation; D006333:Heart Failure / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D006801:Humans; D009154:Mutation; D009206:Myocardium / Q000378:metabolism* / Q000473:pathology; D032383:Myocytes, Cardiac / Q000378:metabolism / Q000473:pathology; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism; D021381:Protein Transport; D015398:Signal Transduction; D025521:Tumor Suppressor Proteins / Q000235:genetics / Q000378:metabolism
chemical_list: D048868:Adaptor Proteins, Signal Transducing; C101410:BIN1 protein, human; D020746:Calcium Channels, L-Type; D018031:Connexin 43; D009687:Nuclear Proteins; D020033:Protein Isoforms; D025521:Tumor Suppressor Proteins