Intercalated Disc-Associated Protein, mXin-alpha, influences surface expression of ITO currents in ventricular myocytes

Fu Chi Chan, Chiao Pei Cheng, Kuo Ho Wu, Yao Chang Chen, Chih Hsiung Hsu, Elisabeth A. Gustafson-Wagner, Jenny Li Chun Lin, Qinchuan Wang, Jim Jung Ching Lin, Cheng I. Lin

Research output: Contribution to journalArticle

Abstract

Mouse Xin-alpha (mXin-alpha) encodes a Xin repeat-containing, actin-binding protein localized to the intercalated disc (ICD). Ablation of mXin-alpha progressively leads to disrupted ICD structure, cardiac hypertrophy and cardiomyopathy with conduction defects during adulthood. Such conduction defects could be due to ICD structural defects and/or cell electrophysiological property changes. Here, we showed that despite the normal ICD structure, juvenile mXina-null cardiomyocytes (from 3∼4-week-old mice) exhibited a significant reduction in the transient outward K+ current (ITO), similar to adult mutant cells. Juvenile but not adult mutant cardiomyocytes also had a significant reduction in the delayed rectifier K+ current. In contrast, the mutant adult ventricular myocytes had a significant reduction in the inward rectifier K+ current (IK1) on hyperpolarization. These together could account for the prolongation of action potential duration (APD) and the ease of developing early afterdepolarization observed in juvenile mXin-alpha-null cells. Interestingly, juvenile mXin-alpha-null cardiomyocytes had a notable decrease in the amplitude of intracellular Ca2+ transient and no change in the L-type Ca2+ current, suggesting that the prolonged APD did not promote an increase in intracellular Ca2+ for cardiac hypertrophy. Juvenile mXinalpha-null ventricles had reduced levels of membrane-associated Kv channel interacting protein 2, an auxiliary subunit of ITO, and filamin, an actin cross-linking protein. We further showed that mXin-alpha interacted with both proteins, providing a novel mechanism for ITO surface expression.

Original languageEnglish (US)
Pages (from-to)1425-1442
Number of pages18
JournalFrontiers in Bioscience - Elite
Volume3 E
Issue number4
StatePublished - Jan 6 2011

Keywords

  • Developmental changes
  • Electrophysiology
  • KChIP2
  • L-type Ca current
  • Transient outward K current

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Immunology and Microbiology(all)

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  • Cite this

    Chan, F. C., Cheng, C. P., Wu, K. H., Chen, Y. C., Hsu, C. H., Gustafson-Wagner, E. A., Lin, J. L. C., Wang, Q., Lin, J. J. C., & Lin, C. I. (2011). Intercalated Disc-Associated Protein, mXin-alpha, influences surface expression of ITO currents in ventricular myocytes. Frontiers in Bioscience - Elite, 3 E(4), 1425-1442.