Microtubule-Mediated Defects in Junctophilin-2 Trafficking Contribute to Myocyte T-Tubule Remodeling and Ca Handling Dysfunction in Heart Failure
نویسندگان
چکیده
Division of Cardiovascular Medicine, Dept of Internal Medicine, University of Iowa Carver College of Medicine, Iowa City, IA; Shanghai First People’s Hospital, Shanghai Jiaotong University, Shanghai, China; Division of Cardiovascular Surgery, Mayo Clinic, Rochester, MN; Dept of Pharmacology, College of Basic Medicine, Anhui Medical University, Hefei, China; Dept of Physiology & Biophysics, University of Washington School of Medicine, Seattle, WA; Dept of Veterans Affairs Medical Center, Iowa City, IA; Dept of Molecular Physiology and Biophysics, Baylor College of Medicine, Houston, TX; Dept of Molecular Physiology and Biophysics, University of Iowa Carver College of Medicine, Iowa City, IA
منابع مشابه
Microtubule-mediated defects in junctophilin-2 trafficking contribute to myocyte transverse-tubule remodeling and Ca2+ handling dysfunction in heart failure.
BACKGROUND Cardiac dysfunction in failing hearts of human patients and animal models is associated with both microtubule densification and transverse-tubule (T-tubule) remodeling. Our objective was to investigate whether microtubule densification contributes to T-tubule remodeling and excitation-contraction coupling dysfunction in heart disease. METHODS AND RESULTS In a mouse model of pressur...
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Cardiac myocytes from the mdx mouse, the mouse model of Duchenne muscular dystrophy, exhibit t-tubule disarray and increased calcium sparks, but a unifying molecular mechanism has not been elucidated. Recently, improper trafficking of junctophilin-2 on an altered microtubule network caused t-tubule derangements and calcium mishandling in a pressure-overload heart failure model. Mdx cardiac myoc...
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BACKGROUND A highly organized transverse tubule (T-tubule) network is necessary for efficient Ca(2+)-induced Ca(2+) release and synchronized contraction of ventricular myocytes. Increasing evidence suggests that T-tubule remodeling due to junctophilin-2 (JP-2) downregulation plays a critical role in the progression of heart failure. However, the mechanisms underlying JP-2 dysregulation remain i...
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Right ventricular (RV) failure (RVF) is the main cause of death in patients with pulmonary artery hypertension (PAH). Sildenafil, a phosphodiesterase type 5 inhibitor, was approved recently for treatment of PAH patients. However, the mechanisms underlying RV contractile malfunction and the benefits of sildenafil on RV function are not well understood. We aimed to investigate the following: (1) ...
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BACKGROUND Junctophilin-2 (JPH2) is the primary structural protein for the coupling of transverse (T)-tubule associated cardiac L-type Ca channels and type-2 ryanodine receptors on the sarcoplasmic reticulum within junctional membrane complexes (JMCs) in cardiomyocytes. Effective signaling between these channels ensures adequate Ca-induced Ca release required for normal cardiac contractility. D...
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