Reduction in density of transverse tubules and L-type Ca2+ channels in canine tachycardia-induced heart failure

He, Jia‐Qiang; Conklin, Matthew W.; Foell, Jason D.; Wolff, Matthew R.; Haworth, Robert A.; Coronado, Roberto; Kamp, Timothy J.

doi:10.1016/s0008-6363(00)00256-x

Cited by 277 publications

(246 citation statements)

References 41 publications

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“…Schroder et al (39) found that single Ca 2ϩ channels exhibited increased availability and opening probability in cells isolated from failing human hearts, but whole cell I Ca,L did not show significant differences, when compared with nonfailing cells, in agreement with a previous report in humans (27). Recently, it has been found that the L-type Ca 2ϩ channel number is reduced and channel open times are increased in ventricular cells from pacing-induced canine failing hearts, so that overall I Ca,L density is unchanged (10). The results of the present study showed no significant change in I Ca,L density and kinetics in cells from the endocardium, midmyocardial layer, and epicardium, consistent with other reports in the same model and species (13).…”

Section: Discussionsupporting

confidence: 91%

Transmural action potential and ionic current remodeling in ventricles of failing canine hearts

Lau

Ducharme

et al. 2002

American Journal of Physiology-Heart and Circulatory Physiology

225

187

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action potential and ionic current remodeling in ventricles of failing canine hearts. Am J Physiol Heart Circ Physiol 283: H1031-H1041, 2002. First published May 30, 2002 10.1152/ ajpheart.00105.2002.-Heart failure (HF) produces important alterations in currents underlying cardiac repolarization, but the transmural distribution of such changes is unknown. We therefore recorded action potentials and ionic currents in cells isolated from the endocardium, midmyocardium, and epicardium of the left ventricle from dogs with and without tachypacing-induced HF. HF greatly increased action potential duration (APD) but attenuated APD heterogeneity in the three regions. Early afterdepolarizations (EADs) were observed in all cell types of failing hearts but not in controls. Inward rectifier K ϩ current (IK1) was homogeneously reduced by ϳ41% (at Ϫ60 mV) in the three cell types. Transient outward K ϩ current (Ito1) was decreased by 43-45% at ϩ30 mV, and the slow component of the delayed rectifier K ϩ current (IKs) was significantly downregulated by 57%, 49%, and 58%, respectively, in epicardial, midmyocardial, and endocardial cells, whereas the rapid component of the delayed rectifier K ϩ current was not altered. The results indicate that HF remodels electrophysiology in all layers of the left ventricle, and the downregulation of IK1, Ito1, and IKs increases APD and favors occurrence of EADs. heterogeneity; early afterdepolarizations; congestive heart failure; arrhythmias

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Section: Discussionsupporting

confidence: 91%

Transmural action potential and ionic current remodeling in ventricles of failing canine hearts

Lau

Ducharme

et al. 2002

American Journal of Physiology-Heart and Circulatory Physiology

225

187

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“…Such knowledge is in great need for effective development of new diagnostic, prognostic, and therapeutic tools for HF, an endstage cardiac disease with poor clinical prognosis. The pathophysiologic hallmark of HF is a weakened cardiac calcium transient (Gómez et al, 1997;Litwin et al, 2000;Gómez et al, 2001), which can be attributed to t-tubule remodeling (Lyon et al, 2009;Louch et al, 2010;Wei et al, 2010) and dyad uncoupling (Gómez et al, 1997;Gómez et al, 2001;He et al, 2001;Louch et al, 2006;Bito et al, 2008;Louch et al, 2010). T-tubule remodeling marks the transition from hypertrophy to failure (Wei et al, 2010), contributing to the progression of HF (see reviews in (Brette and Orchard, 2003;Brette and Orchard, 2007;Louch et al, 2010;Ferrantini et al, 2013;Guo et al, 2013;Ibrahim and Terracciano, 2013)).…”

Section: Bin1 In Heart Failure Progressionmentioning

confidence: 99%

Cardiac BIN1 (cBIN1) is a regulator of cardiac contractile function and an emerging biomarker of heart muscle health

Zhou

Hong

2016

Sci. China Life Sci.

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In recent decades, a cardiomyocyte membrane scaffolding protein bridging integrator 1 (BIN1) has emerged as a critical multifunctional regulator of transverse-tubule (t-tubule) function and calcium signaling in cardiomyocytes. Encoded by a single gene with 20 exons that are alternatively spliced, more than ten BIN1 protein isoforms are expressed with tissue and disease specificity. The recently discovered cardiac alternatively spliced isoform BIN1 (cBIN1 or BIN1+13+17)plays a crucial role in organizing membrane microfolds within cardiac t-tubules. These cBIN1-induced microfolds form functional dyad microdomains by trafficking L-type calcium channels (LTCC) to t-tubule membrane and recruiting ryanodine receptors (RyR) to junctional sarcoplasmic reticulum membrane. When cBIN1 is transcriptionally reduced as occurs in heart failure, cBIN1-microfolds are disrupted and fail to form LTCC and RyR couplons. As a result, impaired dyad formation limits excitation-contraction coupling thus cardiac contractility, and accumulation of orphaned leaky RyRs outside of dyads increases ventricular arrhythmias. Reduced myocardial BIN1 in heart failure is also detectable at the blood level, and plasma BIN1 level predicts heart failure progression and future arrhythmias in cardiomyopathy patients. Here we will review the recent progress in BIN1-related cardiomyocyte biology studies and discuss the diagnostic and predictive values of cBIN1 in future clinical use. heart failure, cBIN1, t-tubules, calcium transient, arrhythmias Citation:Zhou, K., and Hong, T. (2017). Cardiac BIN1 (cBIN1) is a regulator of cardiac contractile function and an emerging biomarker of heart muscle health.

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“…Although the canine tachycardia HF model has been used to characterize pathophysiological changes in HF and to explore the roles of individual genes/ proteins in pathogenesis of HF [9][10][11][12][13][14], genome-wide expression analyses to identify pathways/ networks that underlie the molecular genesis of the HF phenotype in this model have not been performed.…”

Section: Introductionmentioning

confidence: 99%

Transcriptomic profiling of the canine tachycardia-induced heart failure model: global comparison to human and murine heart failure

Zhong

DiSilvestre

et al. 2006

Journal of Molecular and Cellular Cardiology

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Alterations of cardiac gene expression are central to ventricular dysfunction in human heart failure (HF). The canine tachycardia pacing-induced HF model is known to reproduce the main hemodynamic, echocardiographic and electrophysiological changes observed in human HF. In this study, we use this HF model to compare gene expression profiles in the left and right ventricles (LV, RV) of normal and end-stage failing canine hearts and compare the transcription profiles to those in human and murine models of HF. In end-stage HF, the LV exhibits down regulation of genes involved in energy production, cardiac contraction, and modulation of excitation-contraction coupling as compared with normal LV. The majority of transcriptomic changes between normal and end-stage canine HF were shared by the RV and LV. Genes down regulated only in the LV included those involved in aerobic energy production pathways, regulation of actin filament length, and enzymelinked receptor protein signaling pathways. In normal canine hearts, genes encoding specific components of the contractile apparatus exhibit LV-RV asymmetric expression patterns; in failing hearts, cardiac fetal transcription factors MEF2 and MITF and the stress-responsive transcription factor ATF4 showed interventricular differences in expression. The comparison among the canine tachypacing, mouse transgenic, and human HF reveals that human disease involves down regulation of genes in a broad range of biological processes while experimentally induced HF is associated with down regulation of energy pathways, and that human ischemic HF and canine HF share a similar over representation of transcriptional pathways in the up regulated genes. This study provides insights into the molecular pathways leading to end-stage tachycardia-induced HF, and into global transcriptomic differences between the animal HF models and human HF.

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Reduction in density of transverse tubules and L-type Ca2+ channels in canine tachycardia-induced heart failure

Abstract: Cellular remodeling in heart failure results in decreased density of T-tubules and L-type Ca(2+) channels, which contribute to abnormal EC coupling.

Cited by 277 publications

References 41 publications

Transmural action potential and ionic current remodeling in ventricles of failing canine hearts

Transmural action potential and ionic current remodeling in ventricles of failing canine hearts

Cardiac BIN1 (cBIN1) is a regulator of cardiac contractile function and an emerging biomarker of heart muscle health

Transcriptomic profiling of the canine tachycardia-induced heart failure model: global comparison to human and murine heart failure

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