Intercalated Disc-Associated Protein mXinα Influences Surface Expresession of Ito and IK1 Currents in Ventricular Myocytes

• Lin Cheng-I

  Institute of Physiology, National Defense Medical Center

• Chan Fu-Chi

  Institute of Physiology, National Defense Medical Center

• Cheng Chiao-Pei

  Institute of Physiology, National Defense Medical Center

• Wu Kuo-Ho

  Institute of Physiology, National Defense Medical Center

• Chen Yao-Chang

  Institute of Physiology, National Defense Medical Center

• Hsu Chih-Hsiung

  Institute of Physiology, National Defense Medical Center

• A. Gustafson-Wagner Elisabeth

  Department of Biology, University of Iowa

• Li-Chun Lin Jenny

  Department of Biology, University of Iowa

• Wang Qinchuan

  Department of Biology, University of Iowa

• Jung-Ching Lin Jim

  Department of Biology, University of Iowa

抄録

Mouse Xinα (mXinα) encodes a Xin repeat-containing, actin-binding protein localized to the intercalated disc (ICD). Ablation of mXinα 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 mXinα-null cardiomyocytes (from 3∼4-week-old mice) exhibited a significant reduction in the I_to, similar to adult mutant cells. Juvenile but not adult mutant cardiomyocytes also had a significant reduction in the I_K. In contrast, the mutant adult ventricular myocytes had a significant reduction in the I_K1 on hyperpolarization. These together could account for the prolongation of APD and developing EAD observed in juvenile mXinα-null cells. Interestingly, juvenile mXinα-null cardiomyocytes had a notable decrease in the amplitude of intracellular Ca²⁺ transient and no change in the I_Ca,L, suggesting that the prolonged APD did not promote an increase in [Ca²⁺]_i for cardiac hypertrophy. Juvenile mXinα-null ventricles had reduced levels of membrane-associated KChIP2, an auxiliary subunit of I_to, and filamin, an actin cross-linking protein. We further showed that mXinα interacted with both proteins, providing a novel mechanism for I_to surface expression.

収録刊行物

• Journal of Arrhythmia

  Journal of Arrhythmia 27 (Supplement), SS1_4-, 2011

  日本不整脈学会

キーワード

• juvenile vs. adult
• intercalated disc
• transient outward K<SUP>+</SUP> current & inward rectifier K<SUP>+</SUP> current

詳細情報

• CRID: 1390282680222453120
• NII論文ID: 130002130107
• DOI: 10.4020/jhrs.27.ss1_4
• ISSN: 18832148
• ISSN: 18804276
• 本文言語コード: en
• データソース種別:
  • JaLC
  • Crossref
  • CiNii Articles
• 抄録ライセンスフラグ: 使用不可