title: Effects of induced Na+/Ca2+exchanger overexpression on the spatial distribution of L-type Ca2+channels and junctophilin-2 in pressure-overloaded hearts.
abstract: The Na+/Ca2+exchanger 1 (NCX1) is an essential Ca2+efflux system in cardiomyocytes. Although NCX1 is distributed throughout the sarcolemma, a subpopulation of NCX1 is localized to transverse (T)-tubules. There is growing evidence that T-tubule disorganization is a causal event that shifts the transition from hypertrophy to heart failure (HF). However, the detailed molecular mechanisms have not been clarified. Previously, we showed that induced NCX1 expression in pressure-overloaded hearts attenuates defective excitation-contraction coupling and HF progression. Here, we examined the effects of induced NCX1 overexpression on the spatial distribution of L-type Ca2+channels (LTCCs) and junctophilin-2 (JP2), a structural protein that connects the T-tubule and sarcoplasmic reticulum membrane, in pressure-overloaded hearts. Quantitative analysis showed that the regularity of NCX1 localization was significantly decreased at 8 weeks after transverse aortic constriction (TAC)-surgery; however, T-tubule organization and the regularities of LTCC and JP2 immunofluorescent signals were maintained at this time point. These observations demonstrated that release of NCX1 from the T-tubule area occurred before the onset of T-tubule disorganization and LTCC and JP2 mislocalization. Moreover, induced NCX1 overexpression at 8 weeks post-TAC not only recovered NCX1 regularity but also prevented the decrease in LTCC and JP2 regularities at 16 weeks post-TAC. These results suggested that NCX1 may play an important role in the proper spatial distribution of LTCC and JP2 in T-tubules in the context of pressure-overloading.
authors: First Department of Physiology, Kawasaki Medical School, Japan; Department of Cardiovascular Physiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, Japan.
authors: Yoshihiro
authors: Y
authors: Ujihara
authors: First Department of Physiology, Kawasaki Medical School, Japan; Department of Cardiovascular Physiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, Japan.
authors: Satoshi
authors: S
authors: Mohri
authors: Department of Cardiovascular Physiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, Japan. Electronic address: ytanigu@md.okayama-u.ac.jp.
authors: Yuki
authors: Y
authors: Katanosaka
mesh_terms: D000818:Animals; D020746:Calcium Channels, L-Type / Q000378:metabolism*; D006352:Heart Ventricles / Q000378:metabolism*; D017379:Hypertrophy, Left Ventricular / Q000378:metabolism*; D008297:Male; D008565:Membrane Proteins / Q000378:metabolism*; D051379:Mice; D008822:Mice, Transgenic; D008870:Microtubules / Q000378:metabolism*; D009124:Muscle Proteins / Q000378:metabolism*; D032383:Myocytes, Cardiac; D009928:Organ Specificity; D019831:Sodium-Calcium Exchanger / Q000378:metabolism*; D014018:Tissue Distribution; D015854:Up-Regulation
chemical_list: D020746:Calcium Channels, L-Type; D008565:Membrane Proteins; D009124:Muscle Proteins; D019831:Sodium-Calcium Exchanger; C499849:NCX1 protein, mouse; C000589042:JP2 protein, mouse
keywords: Heart failure; Junctophilin-2; L-type Ca(2+) channel; Na(+)/Ca(2+) exchanger 1; Pressure-overloading; Transverse-tubule