© 1996 American Heart Association, Inc.
Articles |
Differential Expression of Voltage-Gated K+ Channel Genes in Left Ventricular Remodeled Myocardium After Experimental Myocardial Infarction
the Cardiology Division, Department of Medicine, State University of New York Health Science Center and Veterans Affairs Medical Center, Brooklyn, NY.
Correspondence to Madhavi Gidh-Jain, Cardiology Division, Veterans Affairs Medical Center, 800 Poly Pl, Brooklyn, NY 11209.
Left ventricular (LV) remodeling after experimental myocardial infarction (MI) is associated with hypertrophy of noninfarcted myocardium and electrophysiological alterations. We have recently shown that post-MI hypertrophied LV myocytes have prolonged action potential duration (APD) and generate triggered activity from early afterdepolarizations. The prolonged APD was attributed to decreased density of the two outward K+ currents, Ito-fast (Ito-f) and Ito-slow (Ito-s), rather than changes in the density and/or kinetics of the L-type Ca2+ current. The changes in ionic current density may be related to alterations in the expression and levels of ion channel proteins. To test this hypothesis, rats underwent either left anterior descending coronary artery (LAD) ligation (post-MI group [n=10]) or sham surgery (sham group [n=10]). Three weeks later, transcripts from the noninfarcted LV myocardium in the post-MI group (n=6) and LV myocardium of the sham group (n=6) were analyzed by RNase protection assay. Expressions of five K+ channel subunit mRNAs (Kv1.2, Kv1.4, Kv1.5, Kv2.1, and Kv4.2) reported in the rat ventricle were analyzed. Compared with the sham group, expressions of Kv1.4, Kv2.1 (putative Ito-s), and Kv4.2 (putative Ito-f) channel subunit mRNAs were significantly decreased by 60% (P<.03), 54% (P<.005), and 53% (P<.002), respectively, in the post-MI group. There was no significant change in the Kv1.2 and Kv1.5 mRNA levels. Western blotting demonstrated a similar decrease in the Kv2.1 and Kv4.2 immunoreactive protein levels (43% [P<.03] and 67% [P<.003], respectively [n=4]) and no significant change in Kv1.5 immunoreactive protein level. Our results strongly correlate with the electrophysiological findings in this model and show that transcriptional regulation in the post-MI remodeled rat LV is distinct for each voltage-gated K+ channel subunit. These findings provide, at least in part, the molecular basis for the electrophysiological alterations observed in this model.
Key Words: cardiac hypertrophy • myocardial infarction • K+ channel • mRNA levels
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