Intercalated Disc-Associated Protein mXina Influences Surface Expresession of Ito and K1 Currents in Ventricular Myocytes

Cheng I. Lin, 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

Research output: Contribution to journalArticlepeer-review

Abstract

Mouse Xina (mXina) encodes a Xin repeat-containing, actin-binding protein localized to the intercalated disc (ICD). Ablation of mXinaprogressively 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 mXin α-null cardiomyocytes (from 3~4-week-old mice) exhibited a significant reduction in the Ito, similar to adult mutant cells. Juvenile but not adult mutant cardiomyocytes also had a significant reduction in the IK. In contrast, the mutant adult ventricular myocytes had a significant reduction in the IK1 on hyperpolarization. These together could account for the prolongation of APD and developing EAD observed in juvenile mXina-null cells. Interestingly, juvenile mXina-null cardiomyocytes had a notable decrease in the amplitude of intracellular Ca2+ transient and no change in the h.L, suggesting that the prolonged APD did not promote an increase in [Ca2+]I for cardiac hypertrophy. Juvenile mXina-null ventricles had reduced levels of membrane-associated KChIP2, an auxiliary subunit of Ito, and filamin, an actin cross-linking protein. We further showed that mXin α interacted with both proteins, providing a novel mechanism for Ito surface expression.

Original languageEnglish (US)
Pages (from-to)241
Number of pages1
Journaljournal of arrhythmia
Volume27
Issue number4
DOIs
StatePublished - 2011
Externally publishedYes

Keywords

  • intercalated disc
  • juvenile vs. adult
  • transient outward K current & inward rectifier K current

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

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