BACKGROUND AND PURPOSE: Recent clinical data suggest beneficial effects of 
ivabradine, a specific heart rate (HR)-lowering drug, in heart failure patients. 
However, the mechanisms responsible for these effects have not been completely 
clarified. Thus, we investigated functional/molecular changes in I(f), the 
specific target of ivabradine, in the failing atrial and ventricular myocytes 
where this current is up-regulated as a consequence of maladaptive remodelling.
EXPERIMENTAL APPROACH: We investigated the effects of ivabradine (IVA; 10 
mg·kg(-1) ·day(-1) for 90 days) on electrophysiological remodelling in left 
atrial (LA), left ventricular (LV) and right ventricular (RV) myocytes from 
post-mycardial infarcted (MI) rats, with sham-operated (sham or sham + IVA) rats 
as controls. I(f) current was measured by patch-clamp; 
hyperpolarization-activated cyclic nucleotide-gated (HCN) channel isoforms and 
microRNA (miRNA-1 and miR-133) expression were evaluated by reverse 
transcription quantitative PCR.
KEY RESULTS: Maximal specific conductance of I(f) was increased in MI, versus 
sham, in LV (P < 0.01) and LA myocytes (P < 0.05). Ivabradine reduced HR in both 
MI and sham rats (P < 0.05). In MI + IVA, I(f) overexpression was attenuated and 
HCN4 transcription reduced by 66% and 54% in LV and RV tissue, respectively, 
versus MI rats (all P < 0.05). miR-1 and miR-133, which modulate 
post-transcriptional expression of HCN2 and HCN4 genes, were significantly 
increased in myocytes from MI + IVA.
CONCLUSION AND IMPLICATION: The beneficial effects of ivabradine may be due to 
the reversal of electrophysiological cardiac remodelling in post-MI rats by 
reduction of functional overexpression of HCN channels. This is attributable to 
transcriptional and post-transcriptional mechanisms.