The sodium-calcium exchange serves as a major mechanism for intracellular calcium extrusion and has previously been suggested to be essential for normal pacemaking [1]. However, increases in NCX1 expression (e.g. in end-stage heart failure) are also associated with increased susceptibility to arrhythmias. If such changes in calcium regulation are evident with ageing it may similarly underlie the known increased predisposition to arrhythmias in the elderly. Male Wistar rats at the ages of 6 months (young), 12 months (adult) and 24 months (old) (n=5 per group) were sacrificed by anaesthetic overdose via intraperitoneal injection. The SAN region of the heart was removed and intrinsic pacemaker activity recorded in bicarbonate-buffered saline at 37°C, under control conditions and in the presence of incrementing concentrations of nifedipine (0.1µm, 1µm, 3µm, 10µm and 30µm) to block L-type calcium channels (Cav1.2). Western blot and immunocytochemistry assessed expression of Cav1.2, sodium-calcium exchanger (NCX1) and plasma membrane calcium ATPase pumps (PMCA) within the SAN. Data are mean±SEM percentages relative to the average young control values, compared by ANOVA followed by Students t-test with Bonferroni’s adjustment (p<0.05). There was a significant age-associated decline in heart rate from young to old (young 100±3.4% vs. old 78±4.9%), accompanied by a change in sensitivity to nifedipine from young to old. The EC50 for nifedipine did not differ significantly between ages (average 1.31 µM) but the Hill slope changed from -1.1 in the young to -3.1 in the old. For the young a maximum dose of 30µm was required to stop pacemaker activity compared with a maximum dose of 3µm in the old. Within the SAN protein expression of Cav1.2 and PMCA significantly decreased from young to old (Cav1.2 young 100±14.6% vs. old 61±13.9%: PMCA young 100±5.7% vs. 78±1.7%), whereas NCX1 expression increased in the old heart (young 100±5.3% vs. old 171±13.6%). In contrast in the right atrial muscle we observed similar changes in Cav1.2 (young 100±12.5% vs. old 53±11.8%) and PMCA (young 100±9.2% vs. 64±4.6%) but there was also a significant decrease in NCX1 expression (young 100±15.3% vs. old 51±7.9%). In conclusion significant alterations in function of the SAN and sensitivity to calcium channel blockade were observed in old age accompanied by changes in the expression of calcium regulatory proteins. The observed changes may be instrumental in rendering the heart more susceptible to arrhythmias.