Background: Nav1.5 is the predominantly expressed voltage-gated sodium channel isoform in the heart, responsible for the upstroke of the action potential. Changes in sodium currents may lead to an increased frequency of arrhythmogenic episodes.1 Aim: To investigate the protein expression of Nav1.5 in the right atrial appendage of tissue from patients in sinus rhythm compared with those diagnosed with atrial fibrillation (AF). Methods: Tissue from the right atrial appendage was obtained from patients undergoing routine cardiac surgery; coronary artery bypass or valve repair (NHS-REC approval 197493). The two patient groups of ‘sinus rhythm’ and ‘AF’ were matched on age, operation-type, and their co-morbidities. Expression of Nav1.5 protein was quantified by specific protein-directed primary antibody (Alomone, Israel) coupled with a secondary antibody conjugated to HRP for western blot (Abcam, UK), or Alexa Fluor 488 (ThermoFisher, UK) for immunohistochemistry with confocal microscopy (LSM 710 Zeiss, UK).2 Densities were quantified using Image J software. Results: Arranged in chronological age order (43 – 87 years of age) we demonstrated a negative correlation between increasing age and Nav1.5 protein expression (n = 26, Pearson correlation coefficient of -0.25): The gradient demonstrates a decline of 9 % Nav1.5 protein per decade of ageing. Comparison of ‘matched patients’ (age range 63 – 80 years; mean 72 years per group) revealed that those diagnosed with AF expressed 50% less Nav1.5 protein when compared with patients in normal sinus rhythm (n=7, t-test P<0.001). This novel finding using the technique of western blot was reflected by immunocytochemistry, as elderly patient tissue showed a lower density of labelled Nav1.5 protein with a florescent tag than their younger counterparts where label was strongly visualised at the t-tubules and intercalated disks. Conclusion: With increasing chronological age of the patient from which the right atrial tissue was derived we determined reduced expression of Nav1.5 protein, and furthermore Nav1.5 protein expression was reduced in AF patient tissue when compared with age-matched tissue from patients in sinus rhythm: Thus, demonstrating a reduction in Nav1.5 protein expression contributes to susceptibility of arrhythmias in the elderly heart.