The significant role of Na+/Ca2+ exchanger 1 on local Ca2+ control beneath T-tubule membrane

Yoshihiro Ujihara, Keiichiro Iwasaki, Satomi Takatsu, Ken Hashimoto, Keiji Naruse, Satoshi Mohri, Yuki Katanosaka

Research output: Contribution to journalArticle

Abstract

Na+/Ca2+ exchanger (NCX1) is essential Ca2+ regulator of myocyte Ca2+ homeostasis and specially localized at transverse tubules (T-tubules) membrane. T-tubules are invaginations of the sarcolemma and critical for myocyte contraction, especially as the main site of excitation-contraction coupling. Therefore, T-tubule disorganization is linked to decreased contractility in heart failure, but the molecular mechanism is not clear. We analyzed the alteration of T-tubule structure and Ca2+ handling during the progression of heart failure after transverse aortic constriction (TAC)-surgery, using cardiac-specific and inducible NCX1 transgenic mice. In progression of cardiac dysfunction, sarcoplasmic reticulum Ca2+ ATPase and NCX1 activity were down-regulated before T-tubule disorganization. The inducing NCX1 overexpression after TAC-surgery prevented T-tubule disorganization and contractile dysfunction under prolonged pressure-overload, with improvement of myocyte Ca2+ handling. These results suggest that local Ca2+ control beneath the T-tubule membrane is crucial for the maintenance of myocyte structure and function, in which NCX1 has a pivotal role.

Original languageEnglish
Pages (from-to)O-212-O-213
JournalTransactions of Japanese Society for Medical and Biological Engineering
Volume52
DOIs
Publication statusPublished - Aug 17 2014

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Keywords

  • Calcium
  • Cardiomyocyte
  • Heart failure
  • Hypertrophy
  • Na/Ca exchanger
  • T-tubule

ASJC Scopus subject areas

  • Biomedical Engineering

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