Altered excitation-contraction coupling in myocytes from remodeled myocardium after chronic myocardial infarction

Young Kwon Kim, Song Jung Kim, Christopher M. Kramer, Atsuko Yatani, Gen Takagi, Sunil Mankad, Gyula P. Szigeti, Deepak Singh, Sanford P. Bishop, Richard P. Shannon, Dorothy E. Vatner, Stephen F. Vatner

Research output: Article

31 Citations (Scopus)

Abstract

Following myocardial infarction (MI), the left ventricle undergoes progressive dilatation and eccentric hypertrophy, i.e., remodeling, which is greater in the adjacent than the remote region. The cellular mechanisms underlying these regional differences were studied. One (n = 5) and 8 weeks (n = 8) after anteroapical MI in sheep, cardiac myocytes were isolated from the adjacent and remote regions. At 8 weeks after MI, myocyte function in the remote region was not different from values either in sham controls (n = 3) or animals 1 week after MI. At 8 weeks after MI, myocyte contractile function (% contraction) was decreased, P < O.01, in the adjacent region (6.4 ± 0.4%), as compared with the remote region (8.8 ± 0.5%) and was associated with decreased amplitude of Ca2+transients (adjacent, 0.69 ± 0.09 v remote, 1.08 ± 0.20, P < 0.05) and L-type Ca2+ current density (adjacent, 3.6 ± 0.2 v remote. 4.8 ± 0.2 pA/pF, P < 0.05). Relaxation was also impaired significantly in myocytes from the adjacent region, associated with decreased protein levels of SERCA2a. The myocytes were hypertrophied more in the adjacent region than the remote region. Furthermore, focal areas of central myofibrillar lysis and increased glycogen deposition were observed in the adjacent region. These results indicate that impaired excitation-contraction coupling underlies dysfunction of myocytes from the adjacent non-infarcted myocardium after chronic MI, even in the absence of heart failure. Hypertrophy is implicated as the mechanism, since these changes were noted at 8 weeks, but not at 1 week after MI.

Original languageEnglish
Pages (from-to)63-73
Number of pages11
JournalJournal of Molecular and Cellular Cardiology
Volume34
Issue number1
DOIs
Publication statusPublished - jan. 1 2002

ASJC Scopus subject areas

  • Molecular Biology
  • Cardiology and Cardiovascular Medicine

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    Kim, Y. K., Kim, S. J., Kramer, C. M., Yatani, A., Takagi, G., Mankad, S., Szigeti, G. P., Singh, D., Bishop, S. P., Shannon, R. P., Vatner, D. E., & Vatner, S. F. (2002). Altered excitation-contraction coupling in myocytes from remodeled myocardium after chronic myocardial infarction. Journal of Molecular and Cellular Cardiology, 34(1), 63-73. https://doi.org/10.1006/jmcc.2001.1490