Objectives: Firstly, to compare effects of adenosine on membrane potential and refractoriness in AV nodal and atrial cells. Secondly, to assess the contribution of the effects of adenosine on IKAdo and ICaL to its effects on the functional electrophysiological properties in the two cell types.
Methods: The whole cell patch clamp technique was used to record action potentials and ion currents in AV nodal and left atrial myocytes isolated enzymatically from rabbit hearts.
Results: Adenosine (10 microM) caused similar hyperpolarisation and shortening of the action potential duration (APD) in both cell types: maximum diastolic potential was hyperpolarised from -59 +/- 3 to -66 +/- 2 and from -70 +/- 2 to -76 +/- 2 mV (mean +/- SEM) and APD90 was shortened by 31 +/- 4 and 30 +/- 7% in AV nodal (n = 14) and atrial cells (n = 8), respectively. Adenosine shortened the effective refractory period (ERP) in atrial cells, from 124 +/- 15 to 98 +/- 14 ms (n = 8). In contrast, ERP in AV nodal cells was not significantly affected (112 +/- 13 vs. 102 +/- 12 ms, n = 14), and post-repolarization refractoriness was prolonged. By contrast, current injection, to induce an equal degree of hyperpolarisation to that produced by adenosine, shortened APD and ERP in both cell types, suggesting an additional action of adenosine in AV nodal cells. Adenosine (10 microM) did not affect peak ICaL in AV nodal cells, but significantly altered the biexponential time course of recovery of ICaL from inactivation. The proportion of recovery in the fast phase (time constant, tau = 102 +/- 10 ms) was reduced from 71 +/- 3 to 55 +/- 5%, with shift to the slow phase (tau = 858 +/- 168 ms), without altering tau in either phase. A similar effect of adenosine was seen in left atrial cells.
Conclusion: Adenosine caused hyperpolarisation, APD-shortening and slowing of recovery of ICaL from inactivation, in both AV nodal and atrial cells, but prolonged post-repolarisation refractoriness in AV nodal cells only. This differential effect of adenosine on refractoriness in the two cell types could not be explained by effects on IKAdo, but may be due to slowed reactivation of ICaL, which is the predominant inward current in AV nodal but not left atrial cells.