The QT interval of the cardiac ECG is frequently increased in heart failure, suggesting ion channel remodelling which has proarrhythmic consequences. The aim of this study was to determine the changes that occur from the in vivo level, down to the level of the ion channel that may contribute to arrhythmogenesis. Heart failure was induced by aortic coarctation, animals were anaesthetised with an intramuscular injection 70 mg kg^-1 medetomidine- 7 mg kg^-1 ketamine. Carprofen analgesic (5 mg kg^-1) was administered pre -operatively. Animals were humanely killed with pentobarbitone sodium (200 mg ^kg-1) administered intraperitoneally at the onset of symptoms of heart failure. The ferret ECG, in lead II configuration, was recorded and analysis of QT interval duration showed 19% increase in the interval in congestive heart failure (CHF) (n=sham, 3; CHF, 4). Action potentials were recorded under current clamp from sham and CHF endocardial and epicardial isolated myocytes and duration measured to 90% repolarisation. An increase in the APD in the endocardial region of the left ventricle (LV) (P<0.01) correlated with a decrease in I_to current density, recorded under whole-cell patch clamp, in the region (P< 0.05; n= sham, 25; CHF, 16). Western blot analysis of the protein constituents of both Ito “fast” and “slow” was performed in the sham and CHF ferret tissue. Kv4.2 and Kv4.3 constitute the “fast” component of I_to in this model. Analysis of full thickness LV protein preparations revealed that Kv4.2 expression was unchanged but there was an increase in total Kv4.3 in CHF (P=0.03; n= sham, 8; CHF, 8). Western blot analysis was also performed on sham and CHF ferret endocardial and epicardial protein preparations and densitometry analysis revealed down-regulation Kv4.2 in the endocardial region whereas Kv4.3 expression was unchanged (P=0.006; n= sham, 3-4; CHF, 4). Furthermore, there was no change in the expression KChIP2b, the β- subunits to the Kv4 channels in this model. Analysis of transmural Kv1.4 expression, the “slow” component of I_to in the ferret, revealed a decrease in expression in the endocardial region of the CHF ferrets relative to sham controls (P=0.03; n= sham, 4; CHF, 4). In conclusion, the changes in protein expression for Kv4.2, Kv4.3 and Kv1.4 may contribute to the electrical remodelling described above and provide a substrate for arrhythmias in CHF.