Ionic basis of a differential effect of adenosine on refractoriness in rabbit AV nodal and atrial isolated myocytes

Objectives: Firstly, to compare effects of adenosine on membrane potential and refractoriness in AV nodal and atrial cells. Secondly, to assess the co ntribution of the effects of adenosine on I-KAdo and I-CaL to its effects o n the functional electrophysiological properties in the two cell types. Met hods: The whole cell patch clamp technique was used to record action potent ials and ion currents in AV nodal and left atrial myocytes isolated enzymat ically from rabbit hearts. Results: Adenosine (10 mu M) caused similar hype rpolarisation and shortening of the action potential duration (APD) in both cell types: maximum diastolic potential was hyperpolarised from -59+/-3 to -66+/-7 and from -70+/-2 to -76+/-2 mV (mean+/-SEM) and APD(90) was shorte ned by 31+/-4 and 30+/-7% in AV nodal (n=14) and atrial cells (n=8), respec tively. 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 cel ls was not significantly affected (112+/-13 vs. 102+/-12 ms, n=14), and pos t-repolarisation refractoriness was prolonged. By contrast, current injecti on, to induce an equal degree of hyperpolarisation to that produced by aden osine, shortened APD and ERP in both cell types, suggesting an additional a ction of adenosine in AV nodal cells. Adenosine (10 mu M) did not affect pe ak I-CaL in AV nodal cells, but significantly altered the biexponential tim e course of recovery of I-CaL from inactivation. The proportion of recovery in the East 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 alter ing tau in either phase. A similar effect of adenosine was seen in left atr ial cells. Conclusion: Adenosine caused hyperpolarisation, APD-shortening a nd slowing of recovery of I-CaL from inactivation, in both AV nodal and atr ial cells, but prolonged post-repolarisation refractoriness in AV nodal cel ls only. This differential effect of adenosine on refractoriness in the two cell types could not be explained by effects on I-KAdo, but may he due to slowed reactivation of I-CaL, which is the predominant inward current in AV nodal but not left atrial cells. (C) 1999 Elsevier Science B.V. All rights reserved.