Many heart failure patients die of bradyarrhythmias, presumably from dysfunction of the cardiac conduction system – insight into this has the potential to improve the outcome of patients affected. Here we studied the cardiac conduction system in rabbits with congestive heart failure (CHF). Male New Zealand White rabbits (2500-3000g) were anaesthetised with ketamine and isoflurane. Aortic incompetence was induced by inserting a catheter through the valve leaflets to cause LV volume overload. Then pressure overload was introduced by placing a silver clip (internal diameter 2.44 mm) just above right renal artery, 3 weeks later. The control group underwent sham procedures. The study was conducted in accordance with the Guide for the Care and Use for Laboratory Animals and approved by the local animal research ethics committee. By the end of 8 weeks, the rabbits showed significant LV hypertrophy, diminished LV fractional shortening and increased LV internal dimension. ECG recording after autonomic blockade showed that the intrinsic heart rate was slower and the RR interval was inversely related to fractional shortening (R2=0.680; P<0.05), indicating dysfunction of the sinoatrial node in the CHF group. Additionally, we found significant increases in the PR interval (by 22%; P=0.001) and QRS duration (by 26%; P=0.02), which evidenced dysfunction of the atrioventricular node and His-Purkinje system. Expression of ion channels (and related molecules studied) was studied at the mRNA and protein levels using quantitative PCR and immunohistochemistry. mRNA expression of 48%, 80% and 33% of 33 ion channels etc. studied was significantly decreased in the sinoatrial node (SAN), left Purkinje fibres and right Purkinje fibres, respectively. mRNA expression in the working myocardium, however, was less affected and only 21%, 3% and 6% of ion channels etc. changed in the LV muscle, right ventricular muscle and right atrial muscle. We observed marked reductions in the SAN in the expression of mRNA for funny channels (HCN1 and HCN4 by 36 and 87%), Ca2+ channels (Cav1.2 and Cav1.3 by 51% and 56%) and K+ channels (Kv1.5, Kir2.1, Kir2.2, ERG and KvLQT1 by 50-86%). Furthermore, the SAN had significantly less mRNA for HCN4 (45%), Ca2+-handling proteins (NCX1 by 37% and RYR2 by 34%) and gap junction protein (Cx40 by 42%). At the protein level, HCN4 was reduced by 45%, NCX1 by 33%, RYR2 by 34% and Cx40 by 43%. Many of these changes could contribute to the slowing of the pacemaker activity of the SAN. In conclusion, our study shows that CHF causes widespread remodelling of ion channels in the cardiac conduction system and, in particular, the SAN, which may contribute to bradyarrhythmic death in heart failure patients.