An Update on Channelopathies

Webster, Gregory; Berul, Charles I.

doi:10.1161/circulationaha.111.060343

Cited by 57 publications

(20 citation statements)

References 143 publications

(136 reference statements)

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“…QT duration is primarily regulated by the function of ion channels and these ion channels are modulated by changes in the activity of interacting molecules and it becomes increasingly clear that the interaction of many components finally determines the electrophysiological properties of the heart [29]. This tight regulation of QT-duration is essential for general heart function to prevent potentially fatal arrhythmias and on the other hand these properties have to be fine-tuned to the functional requirements of a species.…”

Section: Discussionmentioning

confidence: 99%

MiRNA-1/133a Clusters Regulate Adrenergic Control of Cardiac Repolarization

et al. 2014

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The electrical properties of the heart are primarily determined by the activity of ion channels and the activity of these molecules is permanently modulated and adjusted to the physiological needs by adrenergic signaling. miRNAs are known to control the expression of many proteins and to fulfill distinct functions in the mammalian heart, though the in vivo effects of miRNAs on the electrical activity of the heart are poorly characterized. The miRNAs miR-1 and miR-133a are the most abundant miRNAs of the heart and are expressed from two miR-1/133a genomic clusters. Genetic modulation of miR-1/133a cluster expression without concomitant severe disturbance of general cardiomyocyte physiology revealed that these miRNA clusters govern cardiac muscle repolarization. Reduction of miR-1/133a dosage induced a longQT phenotype in mice especially at low heart rates. Longer action potentials in cardiomyocytes are caused by modulation of the impact of β-adrenergic signaling on the activity of the depolarizing L-type calcium channel. Pharmacological intervention to attenuate β-adrenergic signaling or L-type calcium channel activity in vivo abrogated the longQT phenotype that is caused by modulation of miR-1/133a activity. Thus, we identify the miR-1/133a miRNA clusters to be important to prevent a longQT-phenotype in the mammalian heart.

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Section: Discussionmentioning

confidence: 99%

MiRNA-1/133a Clusters Regulate Adrenergic Control of Cardiac Repolarization

et al. 2014

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“…These disorders include long QT syndrome, short QT syndrome, Brugada syndrome, catecholaminergic polymorphic ventricular tachycardia, and sudden unexplained nocturnal death syndrome. The characteristics of each of these arrhythmias have been reviewed elsewhere and include ventricular tachycardia, ventricular fibrillation, and death (Cerrone et al 2012;Webster and Berul 2013). Variants in some of the same ion channel genes have been identified in patients with the "structural" cardiomyopathies, DCM, ARVC, and LVNC, in which ventricular arrhythmias often feature prominently (Tiso et al 2001;Hershberger et al 2008;Shan et al 2008;McNair et al 2011;Mann et al 2012).…”

Section: Left Ventricular Noncompactionmentioning

confidence: 99%

Genetics and Disease of Ventricular Muscle

Fatkin

Seidman

2014

Cold Spring Harbor Perspectives in Medicine

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“…The physiological relevance of this class of molecules is highlighted by the considerable number of human diseases classified as "channelopathies". In most cases, these illnesses are caused by mutations in ion transporter proteins present at the plasma membrane, which affect neuronal, muscular or endocrine tissues, and include many types of epilepsy, ataxia, hypertension, migraines, cardiac arrhythmias and some forms of diabetes mellitus (Kullmann 2010, Rolim, et al 2010, Webster and Berul 2013). In the model plant Arabidopsis thaliana, there are approximately 880 putative cation transporter proteins, which can be classified into 46 different families (Mäser, et al 2001).…”

Section: Importance Of Alkali Metal Transportersmentioning

confidence: 99%

Endocytic regulation of alkali metal transport proteins in mammals, yeast and plants

et al. 2013

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Mulet Salort, JM.; Llopis Torregrosa, V.; Primo Planta, C.; Marques Romero, MC.; Yenush, L. (2013) The relative concentrations of ions and solutes inside cells are actively maintained by several classes of transport proteins, in many cases against their concentration gradient. These transport processes, which consume a large portion of cellular energy, must be constantly regulated. Many structurally distinct families of channels, carriers, and pumps have been characterized in considerable detail during the past decades and defects in the function of some of these proteins have been linked to a growing list of human diseases. The dynamic regulation of the transport proteins present at the cell surface is vital for both normal cellular function and for the successful adaptation to changing environments. The composition of proteins present at the cell surface is controlled on both the transcriptional and post-translational level. Post-translational regulation involves highly conserved mechanisms of phosphorylation-and ubiquitylation-dependent signal transduction routes used to modify the cohort of receptors and transport proteins present under any given circumstances. In this review, we will summarize what is currently known about one facet of this regulatory process: the endocytic regulation of alkali metal transport proteins. The physiological relevance, major contributors, parallels and missing pieces of the puzzle in mammals, yeast and plants will be discussed.

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An Update on Channelopathies

Cited by 57 publications

References 143 publications

MiRNA-1/133a Clusters Regulate Adrenergic Control of Cardiac Repolarization

MiRNA-1/133a Clusters Regulate Adrenergic Control of Cardiac Repolarization

Genetics and Disease of Ventricular Muscle

Endocytic regulation of alkali metal transport proteins in mammals, yeast and plants

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