Atrial fibrillation is the most common cardiac arrhythmia, affecting up to one million people in the UK. Clinical studies have demonstrated that ectopic activity originating from the cardiomyocyte sleeve around the pulmonary vein is an important contributing factor in atrial fibrillation. However the underlying mechanisms of this ectopic activity remain unclear. Recent studies have proposed variations in the properties of ion channels, in particular sodium channels, in atrial and pulmonary vein cardiomyocytes as a potential mechanism. Tetrodotoxin (TTX)-sensitive neuronal sodium channels are found in atrial and ventricular cardiomyocytes; however their presence and function in pulmonary vein cardiomyocytes is unknown. Thus, the main aim of this study was to examine the characteristics of cardiac sodium channels in rat pulmonary vein and atrial cardiomyocytes and to establish whether TTX-sensitive sodium channels are present in the cardiomyocytes from these two regions. Male Sprague-Dawley rats (250-400g) were euthanised by cervical dislocation and the heart and lungs removed en bloc. Thereafter, the pulmonary veins and left atrium were microdissected. Using reverse transcription-polymerase chain reaction, the TTX-sensitive Nav1.1 transcript was found to be present in the rat pulmonary vein but absent from the left atria. The main cardiac sodium channel, Nav1.5 and the four sodium channel associated β-subunits were present in both tissues. Sodium currents were recorded from isolated pulmonary vein and left atrial cardiomyocytes using whole-cell recording techniques. Values are means ± S.E.M. Significance (P<0.05) was calculated by an unpaired t-test. Peak sodium current density at a holding potential of -120 mV with a step to -45 mV was -64.0 ± 4.8 pA/pF, n=10 in pulmonary veins and -64.0 ± 5.9 pA/pF, n=6 in left atrial cardiomyocytes. Voltage of half activation (V½) were similar in pulmonary vein (-55.7 ± 2.3 mV, n=10) and left atrial cardiomyocytes (-58.4 ± 1.4 mV, n=6). There was no significant difference in inactivation V½ in pulmonary vein (-98.3 ± 1.3 mV, n=7) and left atrial (-100.1 ± 2.4 mV, n=6) cardiomyocytes. Application of nM concentrations of TTX, which mainly blocks TTX-sensitive channels, indicated a TTX-sensitive component accounting for approximately 20% of the total sodium current in pulmonary vein but not left atrial cardiomyocytes. The TTX-sensitive current had a KD value of 5.2 nM with a peak current density of -13.0 ± 0.5 pA/pF, n=3 compared to a KD of 650.0 nM and peak current density of -46.8 ± 2.6 pA/pF, n=3 for the TTX-resistant current. Although there was no significant difference in the characteristics of the total sodium current in pulmonary vein and left atrial cardiomyocytes, a variation in sodium channel subtype expression does exist as a TTX-sensitive current was detected in pulmonary vein but not left atrial cardiomyocytes.