start-ver=1.4
cd-journal=joma
no-vol=480
cd-vols=
no-issue=4
article-no=
start-page=564
end-page=569
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2016
dt-pub=201611
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=Effects of induced Na+/Ca2+ exchanger overexpression on the spatial distribution of L-type Ca2+ channels and junctophilin-2 in pressure-overloaded hearts
en-subtitle=
kn-subtitle=
en-abstract=
kn-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.
en-copyright=
kn-copyright=

en-aut-name=UjiharaYoshihiro
en-aut-sei=Ujihara
en-aut-mei=Yoshihiro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
ORCID=

en-aut-name=MohriaSatoshi
en-aut-sei=Mohria
en-aut-mei=Satoshi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=2
ORCID=

en-aut-name=KatanosakaYuki
en-aut-sei=Katanosaka
en-aut-mei=Yuki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=3
ORCID=

affil-num=1
en-affil=Department of Cardiovascular Physiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
kn-affil=

affil-num=2
en-affil=Department of Cardiovascular Physiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
kn-affil=

affil-num=3
en-affil=Department of Cardiovascular Physiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
kn-affil=
en-keyword=Heart failure
kn-keyword=Heart failure
en-keyword=Junctophilin-2
kn-keyword=Junctophilin-2
en-keyword=L-type Ca(2+) channel
kn-keyword=L-type Ca(2+) channel
en-keyword=Na(+)/Ca(2+) exchanger 1
kn-keyword=Na(+)/Ca(2+) exchanger 1
en-keyword=Pressure-overloading
kn-keyword=Pressure-overloading
en-keyword=Transverse-tubule
kn-keyword=Transverse-tubule
END