Obesity is an established risk factor for cardiovascular diseases, including ischaemic heart disease and cerebrovascular disease. Arrhythmias are more prevalent in obese patients compared to their lean counterparts. Data from our group have shown evidence of an increase in arrhythmias in a rat model of obesity: a decrease in sinoatrial and atrioventricular nodal function, increases in atrial and ventricular refractory periods, and an increase in the incidence of ventricular arrhythmias. An increase in arrhythmias in obesity is likely to be the result of a remodelling of the heart and the aim of this study was to measure the expression of ion channels, gap junction channels and Ca2+-handling molecules in lean (control) and obese animals. Male Sprague-Dawley rats (n=20) were randomly assigned to receive either a high-energy diet comprising 60% fat (n=10) or a normal diet comprising 20% fat (n=10) for six months. The final body weights were 861±47 and 681±34 g in the obese and lean groups (Student’s t test, P<0.02). Following sacrifice, hearts were excised and mRNA was extracted from the right atrium (RA), right ventricle (RV) and left ventricle (LV) in the two populations of animals. mRNA expression of 17 targets, including ion channels, a gap junction channel and Ca2+-handling molecules, was measured by quantitative PCR. Of the 17 mRNA targets studied, significant differences between lean and obese rats were noted in four from the RA, 10 from the RV and four from the LV. With regard to the channels carrying the inward current If, we observed an upregulation of HCN2 mRNA (to 2500%), but a downregulation of HCN4 mRNA (to 45%), in the RV of the obese rats. With regard to other channels carrying inward currents, we observed an upregulation of Na+ and Ca2+ channels in the obese rats (Nav1.5, to 613% in the LV; Navβ1, to 1063% in the RV and 2113% in the LV; Cav1.2, to 1590% in the RV and 171% in the LV). We observed diverse changes in channels carrying outward K+ currents (Kir2.1, to 14% in the RA; KChIP2, to 48% in the RV; Kv1.5, to 455% in the RA and 1130% in the RV; Kv4.3, to 22% in the RV; KvLQT1, to 25% in the RV and 242% in the LV). The major gap junction channel Cx43 was downregulated to 13% in the RV of the obese rats. Ca2+-handling molecules were also affected in the obese rats: the Na+/Ca2+ exchanger (NCX1) was upregulated to 574% in the RA and SERCA2a was downregulated to 23% in the RV. We have demonstrated marked remodelling of diverse ion channels, a gap junction channel and Ca2+-handling molecules in the hearts of obese rats and this could be responsible for the increase in arrhythmias in this condition. The changes observed were more marked in the RV, and this may reflect the disproportionate load exerted on this part of the heart by the obese condition. Further studies are required to substantiate our findings at the protein and functional levels