ArticleHeart rhythm2012
BIN1 is reduced and Cav1.2 trafficking is impaired in human failing cardiomyocytes.
Article in Heart rhythm, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 109 papers.
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Who cites it
109 citing papers in PubMed, 161 citations in OpenAlex.
- Aging Disrupts L-type CaCirculation research · 2026Article
- Bridging autophagy and endolysosomal dysfunction: Role of bridging integrator 1 in Alzheimer's disease.Neural regeneration research · 2026Article
- T-tubular remodeling occurs in a cardiomyocyte-autonomous manner following pathological mechanical stiffness exposure.Journal of molecular and cellular cardiology plus · 2026Article
- Phosphoinositide Depletion and Compensatory Phospho-Signaling in Angiotensin II-Induced Heart Disease.Circulation research · 2026Article
- Cardiac Cell Remodeling in Obesity and Diabetes.Handbook of experimental pharmacology · 2026Review
- Stress-Induced calcium mishandling in cardiac (Patho)physiology.Cellular and molecular life sciences : CMLS · 2025Review
- Alternative splicing of the Snap23 microexon is regulated by MBNL, QKI, and RBFOX2 in a tissue-specific manner and is altered in striated muscle diseases.RNA biology · 2025Article
- Novel therapeutic cav1.3-C-terminus normalizes L-type calcium current and ejection fraction in ischemia-induced murine heart failure.Biochemical and biophysical research communications · 2025Article
- A novel transgenic reporter of extracellular acidification in zebrafish elucidates skeletal muscle T-tubule pH regulation.Developmental dynamics : an official publication of the American Association of Anatomists · 2025Article
- Early Stage Morphogenesis of Transverse Tubules in Rat Cardiomyocytes: The Role of pBIN1.Circulation research · 2025Article
- Bend it like BIN1: how a membrane-curving adaptor protein shapes cardiac physiology.American journal of physiology. Heart and circulatory physiology · 2025Review
- Aging reduces the number and function of L-type calcium channels in the membrane of cardiac pacemaker cells.bioRxiv : the preprint server for biology · 2025Article
- Probing the CabioRxiv : the preprint server for biology · 2025Article
- Virally delivered CMYA5 enhances the assembly of cardiac dyads.Nature biomedical engineering · 2025Article
- AAV9-cBIN1 gene therapy rescues chronic heart failure due to ischemic cardiomyopathy in a canine model.Communications medicine · 2025Article
- Design of the First in Human Gene Therapy Trial of TLT-101 for Chronic Heart Failure (FIGHT-HF).JACC. Basic to translational science · 2025Article
- Ion channel traffic jams: the significance of trafficking deficiency in long QT syndrome.Cell discovery · 2025Review
- Mechanistic Relevance of Ventricular Arrhythmias in Heart Failure with Preserved Ejection Fraction.International journal of molecular sciences · 2024Review
- Cardiac bridging integrator 1 gene therapy rescues chronic non-ischemic heart failure in minipigs.NPJ Regenerative medicine · 2024Article
- Nanoscale organization of cardiac calcium channels is dependent on thyroid hormone status.American journal of physiology. Heart and circulatory physiology · 2024Article
49 more citing papers are in PubMed but not listed here.
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Authors and funding
14 authors at 5 institutions in 1 country.
Funding
Abstract
backgroundHeart failure is a growing epidemic, and a typical aspect of heart failure pathophysiology is altered calcium transients. Normal cardiac calcium transients are initiated by Cav1.2 channels at cardiac T tubules. Bridging integrator 1 (BIN1) is a membrane scaffolding protein that causes Cav1.2 to traffic to T tubules in healthy hearts. The mechanisms of Cav1.2 trafficking in heart failure are not known.
objectiveTo study BIN1 expression and its effect on Cav1.2 trafficking in failing hearts.
methodsIntact myocardium and freshly isolated cardiomyocytes from nonfailing and end-stage failing human hearts were used to study BIN1 expression and Cav1.2 localization. To confirm Cav1.2 surface expression dependence on BIN1, patch-clamp recordings were performed of Cav1.2 current in cell lines with and without trafficking-competent BIN1. Also, in adult mouse cardiomyocytes, surface Cav1.2 and calcium transients were studied after small hairpin RNA-mediated knockdown of BIN1. For a functional readout in intact heart, calcium transients and cardiac contractility were analyzed in a zebrafish model with morpholino-mediated knockdown of BIN1.
resultsBIN1 expression is significantly decreased in failing cardiomyocytes at both mRNA (30% down) and protein (36% down) levels. Peripheral Cav1.2 is reduced to 42% by imaging, and a biochemical T-tubule fraction of Cav1.2 is reduced to 68%. The total calcium current is reduced to 41% in a cell line expressing a nontrafficking BIN1 mutant. In mouse cardiomyocytes, BIN1 knockdown decreases surface Cav1.2 and impairs calcium transients. In zebrafish hearts, BIN1 knockdown causes a 75% reduction in calcium transients and severe ventricular contractile dysfunction.
conclusionsThe data indicate that BIN1 is significantly reduced in human heart failure, and this reduction impairs Cav1.2 trafficking, calcium transients, and contractility.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.