Early down-regulation of K+ channel genes and currents in the postinfarction heart.
BACKGROUND
Down-regulation of key K+ channel subunit gene expression and K+ currents is a universal response to cardiac hypertrophy, whatever the cause, including the postmyocardial infarction (post-MI) remodeled heart.


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 tachyarrhythmias (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 Ito-fast(f) and 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 Ito-f and I(K) were significantly decreased in 3-day post-MI LV myocytes compared with sham. The reduced density of Ito 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 Ito-f and I(K) correlated with decreased messenger and protein levels of Kv4.2/Kv4.3 and Kv2.1, respectively.


CONCLUSIONS
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.
Huang
B
B
Department of Medicine, State University of New York Health Science Center, Brooklyn 11203, USA.
Qin
D
D
El-Sherif
N
N
D000200:Action Potentials; D000818:Animals; D015536:Down-Regulation; D004553:Electric Conductivity; D005260:Female; D006321:Heart / Q000503:physiopathology*; D009203:Myocardial Infarction / Q000473:pathology / Q000503:physiopathology*; D009206:Myocardium / Q000473:pathology; D015221:Potassium Channels / Q000235:genetics* / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors; D016277:Ventricular Function, Left
D015221:Potassium Channels