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Early Down‐Regulation of K + Channel Genes and Currents in the Postinfarction Heart
Author(s) -
HUANG BOYU,
QIN DAYl,
ELSHERIF NABIL
Publication year - 2000
Publication title -
journal of cardiovascular electrophysiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.193
H-Index - 138
eISSN - 1540-8167
pISSN - 1045-3873
DOI - 10.1046/j.1540-8167.2000.01252.x
Subject(s) - medicine , ventricle , cardiology , myocyte , myocardial infarction , muscle hypertrophy , endocrinology
Down‐Regulation oi K + Channel Genes and Currents. Introduction: Down‐regulaticn of key K + channel subunit gene expression and K + currents is a universal response to cardiac hypertrophy, whatever the cause, including the postmyocdardial infarction (post‐Ml) remodeled heart. Methods and Results: We investigated the hypothesis that down‐regulation of K + channel genes and currents post‐MI occurs early and before significant remodeled hypertrophy of the noninfarcted myocardium could be detected. We investigated (1) the incidence of induced ventricular tachyar‐rhythmias (VT) in 3‐day post‐MI rat heart; (2) action potential (AP) characteristics of isolated left ventricular (LV) myocytes from sham‐operated and 3‐day post‐MI heart; (3) time course of changes in outward K + currents I to‐fast(f) I k in isolated myocytes from 3‐day and 4‐week post‐MI noninfarcted LV and compared the changes with sham‐operated animals; and (4) changes in the messenger and protein levels of Kv2.1, Kv4.2. and Kv4.3 in the LV and right ventricle of 3‐day post‐MI heart. Sustained VT was induced in 6 of 10 3‐day post‐MI rats and in none of 8 sham rats. The membrane capacitance of myocytes isolated from 3‐day post‐MI noninfarcted LV was not significantly different from control, whereas membrane capacitance 4‐week post‐MI was significantly higher, reflecting the development of hypertrophy. AP duration was increased and the density of I to‐f and I k were significantly decreased in 3‐day post‐MI LV myocytes compared with sham. The reduced density of I to , did not significantly differ in 4‐week post‐MI LV myocytes, whereas the density of I k was decreased further at 4 weeks post‐MI. The changes in I to‐f and I k correlated with decreased messenger and protein levels of Kv4.2/Kv4.3 and Kv2.l, respectively. Conclusion: These results support the hypothesis that down‐regulation of K + channel gene expression and current in the post‐MI LV occurs early and may be dissociated from the slower time course of post‐MI remodeled hypertrophy. These changes may contribute to early arrhythmogenesis of the post‐MI heart.