Previous studies have established that reductions in repolarizing currents occur 
in heart disease and can contribute to life-threatening arrhythmias in 
myocardium. In this study, we investigated whether the thyroid hormone analog 3, 
5-diiodothyropropionic acid (DITPA) could restore repolarizing transient outward 
K(+) current (I(to)) density and gene expression in rat myocardium after 
myocardial infarction (MI). Our findings show that I(to) density was reduced 
after MI (14.0 +/- 1.0 vs. 10.2 +/- 0.9 pA/pF, sham vs. post-MI at +40 mV). mRNA 
levels of Kv4.2 and Kv4.3 genes were decreased but Kv1.4 mRNA levels were 
increased post-MI. Corresponding changes in Kv4.2 and Kv1.4 protein were also 
observed. Chronic treatment of post-MI rats with 10 mg/kg DITPA restored I(to) 
density (to 15.2 +/- 1.1 pA/pF at +40 mV) as well as Kv4.2 and Kv1.4 expression 
to levels observed in sham-operated controls. Other membrane currents (Na(+), 
L-type Ca(2+), sustained, and inward rectifier K(+) currents) were unaffected by 
DITPA treatment. Associated with the changes in I(to) expression, action 
potential durations (current-clamp recordings in isolated single right 
ventricular myocytes and monophasic action potential recordings from the right 
free wall in situ) were prolonged after MI and restored with DITPA treatment. 
Our results demonstrate that DITPA restores I(to) density in the setting of MI, 
which may be useful in preventing complications associated with I(to) 
downregulation.