. Altered sinus nodal and atrioventricular nodal function in freely moving mice overexpressing the A1 adenosine receptor. Am J Physiol Heart Circ Physiol 285: H145-H153, 2003. First published March 13, 2003 10.1152/ ajpheart.01036.2002To investigate whether altered function of adenosine receptors could contribute to sinus node or atrioventricular (AV) nodal dysfunction in conscious mammals, we studied transgenic (TG) mice with cardiac-specific overexpression of the A 1 adenosine receptor (A1AR). A Holter ECG was recorded in seven freely moving littermate pairs of mice during normal activity, exercise (5 min of swimming), and 1 h after exercise. TG mice had lower maximal heart rates (HR) than wild-type (WT) mice (normal activity: 437 Ϯ 18 vs. 522 Ϯ 24 beats/min, P Ͻ 0.05; exercise: 650 Ϯ 13 vs. 765 Ϯ 28 beats/min, P Ͻ 0.05; 1 h after exercise: 588 Ϯ 18 vs. 720 Ϯ 12 beats/min, P Ͻ 0.05; all values are means Ϯ SE). Mean HR was lower during exercise (589 Ϯ 16 vs. 698 Ϯ 34 beats/min, P Ͻ 0.05) and after exercise (495 Ϯ 16 vs. 592 Ϯ 27 beats/min, P Ͻ 0.05). Minimal HR was not different between genotypes. HR variability (SD of RR intervals) was reduced by 30% (P Ͻ 0.05) in TG compared with WT mice. Pertussis toxin (n ϭ 4 pairs, 150 g/kg ip) reversed bradycardia after 48 h. TG mice showed first-degree AV nodal block (PQ interval: 42 Ϯ 2 vs. 37 Ϯ 2 ms, P Ͻ 0.05), which was diminished but not abolished by pertussis toxin. Isolated Langendorffperfused TG hearts developed spontaneous atrial arrhythmias (3 of 6 TG mice vs. 0 of 9 WT mice, P Ͻ 0.05). In conclusion, A 1AR regulate sinus nodal and AV nodal function in the mammalian heart in vivo. Enhanced expression of A 1AR causes sinus nodal and AV nodal dysfunction and supraventricular arrhythmias. heart rate regulation; autonomous nervous system; heart rate variability; sinus node dysfunction; atrioventricular block; atrial fibrillation