Recent in vivo biotelemetry studies have demonstrated rapid reductions in heart rate following administration of the diabetogenic agent streptozotocin (STZ) to young rats and these bradycardic effects of STZ-induced diabetes mellitus (DM) are partially normalized with insulin replacement (Howarth et al., 2005 & 2006). Reductions in beating rate have also been reported in spontaneously beating isolated perfused heart and in atrial preparations suggesting that arrhythmias in diabetes mellitus may be partly caused by intrinsic alteration of sinoatrial node (SAN) function (Howarth & Qureshi, 2006; Kofo-Abayomi & Lucas, 1988). The effects of diabetes on electrical activity and expression levels of mRNA for specific ion channel and gap junction proteins in the SAN have been investigated. Diabetes was induced by a single intraperitoneal injection of STZ (60 mg/kg) administered to young male Wistar rats (200-250g). Experiments were performed 8-10 weeks after treatment. SAN action potentials were measured in spontaneously beating Langendorf perfused heart with a suction electrode. Conduction time and pacemaker cycle length were measured in sino-atrial node preparations with extracellular electrodes. Experiments were performed at 36-37 °C. Expression levels of mRNA for Kv4.2 (Ito4.2), Kv4.3 (Ito4.3), ERG (IKr), KVLQT1 (IKs), NCX1 (INa/Ca), Gja5 (Cx40), Gja1 (Cx43) and Gja7 (Cx45) were measured in SAN and compared with right atrium and right ventricle with real-time quantitative reverse transcription-polymerase chain reaction (real-time RT-PCR). Diabetes was confirmed by a significant elevation of blood glucose (356±21 mg/dl) compared to age-matched controls (66±2 mg/dl). Spontaneous heart rate was significantly (P<0.05)lower in diabetic rats (181±7 BPM) compared to controls (248±12 BPM). SAN action potential duration, measured during repolarization at 50 % and 70 % from peak action potential, were significantly prolonged in diabetic heart compared to controls. The pacemaker cycle length and the sino-atrial conduction time were significantly prolonged in SAN from diabetic heart (415±43 and 12±2 ms) compared to controls (255±7 and 7±1 ms), respectively. Expression levels of mRNA for Kv4.2 (Ito4.2) was significantly reduced and for Kv4.3 (Ito4.3) was significantly increased in right ventricle from diabetic heart. Expression levels of mRNA for Gja7 (Cx45) was significantly increased in SAN from diabetic heart compared to controls. Altered expression of ion transport genes may partly underlie electrophysiological defects in STZ-induced diabetic rat heart.