Atrial fibrillation (AF), the most common sustained arrhythmia, usually arises at the junctions of the left atrium (LA) with the pulmonary veins (PV) (1). The autonomic nervous system is important in AF initiation (2). In rat LA cells, noradrenaline (NA) increases L-type Ca current (ICa), inhibits a steady state K current (IKss) and prolongs action potential duration at 30% repolarization (APD30) (3). It has been suggested that NA may trigger arrhythmic activity in PV cells (4). The aim of this study was to examine the electrophysiology of rat PV cardiomyocytes and their responses to NA in comparison with LA cells. Procedures were approved by local ethics committee and performed in accordance with UK legislation. LA and PV cardiomyocytes were isolated from adult male Wistar rat hearts, superfused with a Tyrode’s solution (37 °C) and subject to whole-cell recording using a ruptured patch-clamp technique. Action potentials were recorded during stimulation at 1 Hz using a nominally Ca-free pipette solution. Whole-cell currents were recorded from a holding potential of -80 mV using a Ca2+-buffered pipette solution. ICa was activated by depolarisation to +10 mV (300 ms) following a pre-pulse to -40 mV to inactivate Na current, and measured as the difference between the peak inward current and the steady-state current at the end of the pulse. IKss was recorded as the outward current on depolarisation to +50 mV. Inward rectifier current (IK1) was measured as the K-dependent inward current following a voltage ramp to -120 mV. NA was applied at 1 μM. Data are presented as mean ± standard error of the mean and were compared by either unpaired or paired t-test. P<0.05 was used as the limit of statistical confidence. Membrane capacitance, an index of cell size, was not different between LA (57.5±1.8 pF, n=125) and PV (58.2±2.2 pF, n=125) cardiomyocytes. In control conditions, there were differences between LA and PV cardiomyocytes in ICa (LA -9.13±0.51 pA/pF, n=29; PV -7.19±0.70 pA/pF, n=26; P=0.0330) and IKss (LA 9.98±0.87 pA/pF; PV 14.28±1.18 pA/pF; P=0.0052). IK1 density was also slightly smaller in PV (-13.17±0.62 pA/pF, n=26) compared with LA (-15.78±0.81 pA/pF, n=50; P=0.0339) cardiomyocytes. However, there were no differences between the cell types in APD30 (LA 7.2±0.5 ms, n=24; PV 6.1±0.6 ms, n=24), APD60 (LA 19.7±1.3 ms; PV 15.5±1.6 ms) or APD90 (LA 51.5±3.0 ms; PV 43.8±3.9 ms). In PV cells, NA had no effect on IK1 or on currents during the ramp at diastolic potentials. NA inhibited PV IKss by 41.9±4.1% (n=23, P<0.0001), similar to LA cells (3). In contrast, NA did not increase ICa in all PV cells. Heterogeneity between PV cells in APD30 prolongation by NA was also observed: of 12 cells, 6 showed no response. PV cardiomyocytes show differences to LA cells and respond heterogeneously to NA.